Baker International Diabetes Institute
Baker International Diabetes Institute
Egger G.,Southern Cross University of Australia |
Egger G.,Center for Health Promotion and Research |
Dixon J.,Baker International Diabetes Institute
Obesity Reviews | Year: 2011
A form of low-grade, systemic inflammation ('metaflammation') is linked to many types of chronic disease. Initially, this was thought to be causally related to weight gain and obesity and a possible explanation of the link between obesity and disease. However, several lifestyle-related inducers of such inflammation, some of which are associated with obesity, but some of which are not, have now been identified. The most common of these have been nutritive related, suggesting that there could still be a relationship, either directly or indirectly, with obesity. Here we provide evidence for non-nutritive inflammatory inducers, providing further support for an earlier suggestion that while obesity, beyond a point, may have a direct link with disease, this may be neither necessary nor sufficient to explain the current epidemic of chronic disease. A more ubiquitous cause encompassing all inflammatory inducers is the modern, post-industrial environment and lifestyles emanating from this. Obesity may thus be more of 'a canary in the mineshaft', warning of bigger global problems, than just a single pathway to modern environmentally driven disease. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.
Ryan A.T.,University of Adelaide |
Feinle-Bisset C.,University of Adelaide |
Kallas A.,University of Adelaide |
Wishart J.M.,University of Adelaide |
And 3 more authors.
American Journal of Clinical Nutrition | Year: 2012
Background: Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and hormone release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. Objective: We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal hormone release, glucose and insulin concentrations, appetite perceptions, and energy intake. Design: Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. Results: Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = 20.51, P < 0.001). Conclusion: The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal hormone release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044. © 2012 American Society for Nutrition.
Egger G.,Australian Lifestyle Medicine Association ALMA |
Egger G.,Southern Cross University of Australia |
Katz D.,The American College |
Katz D.,Yale University |
And 5 more authors.
International Journal of Clinical Practice | Year: 2014
Changes in patterns of living result in changes in the nature and causes of disease. The industrial revolution of the late 18th century, and the technological revolution of the late 20th century are cases in point. The former was associated with a decline in infectious diseases; the latter with an increase in lifestyle and environmentally induced chronic diseases. Health practices are typically modified to deal with such changes, hence the recent rise in interest in lifestyle-oriented forms of clinical practice. © 2014 John Wiley & Sons Ltd.
Backholer K.,Monash University |
Walls H.L.,Monash University |
Magliano D.J.,Monash University |
Magliano D.J.,Baker International Diabetes Institute |
Peeters A.,Monash University
American Journal of Public Health | Year: 2010
In 2008, The Council of Australian Governments set a target to increase by 5% the proportion of Australian adults at a healthy body weight by 2017, over a 2009 baseline. Target setting is a critical component of public health policy for obesity prevention; however, there is currently no context within which to choose such targets. We analyzed the changes in current weight gain that would be required to meet Australian targets. By using transition-based multistate life tables to project obesity prevalence, we found that meeting national healthy weight targets by 2017 will require a 75% reduction in current 5-yearweight gain. A reliable model of future body weight prevalence is critical to set, evaluate, and monitor national obesity targets.
Lassenius M.I.,Folkhalsan Institute of Genetics |
Lassenius M.I.,University of Helsinki |
Pietilainen K.H.,University of Helsinki |
Kaartinen K.,University of Helsinki |
And 15 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN). RESEARCH DESIGN AND METHODS - Serum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation. RESULTS - The MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1. CONCLUSIONS - High serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases. © 2011 by the American Diabetes Association.
PubMed | Baker International Diabetes Institute, Monash University and University of Western Sydney
Type: | Journal: BMC public health | Year: 2016
Tobacco smoking is a major burden on the Australian population in terms of health, social and economic costs. Because of this, in 2008, all Australian Governments agreed to set targets to reduce prevalence of smoking to 10 % by 2018 and subsequently introduced several very strong anti-smoking measures. On this backdrop, we estimated in 2012-13 the impact of several scenarios related to reduction of smoking prevalence to 10 % across the entire Australian population and for below specific ages, on improving life expectancy.Using the risk percentiles method the Australian Diabetes, Obesity and Lifestyle (AUSDIAB) baseline survey and the Australian Bureau of Statistics (ABS) age-sex specific death counts were analyzed.Amongst men the gains in life expectancy associated with 10 % smoking prevalence are generally greater than those of women with average life expectancy for men increasing by 0.11 to 0.41 years, and for women by 0.12 to 0.29 years. These are at best 54 % and 49 % for men and women of the gains achieved by complete smoking cessation. The gains plateau for interventions targeting those <70 and <80 years. Amongst smokers the potential gains are much greater, with an increase in average life expectancy amongst men smokers of 0.43 to 2.08 years, and 0.73 to 2.05 years amongst women smokers. These are at best 46 % and 38 % for men and women smokers of the gains achieved by complete smoking cessation.The estimated optimum gain in life expectancy is consistent with potentially moderate gains which occur when both men and women below 60 years are targeted to reduce smoking prevalence to 10 %.
Bierhaus A.,University of Heidelberg |
Fleming T.,University of Heidelberg |
Stoyanov S.,University of Heidelberg |
Leffler A.,Hannover Medical School |
And 33 more authors.
Nature Medicine | Year: 2012
This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na v 1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na v 1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na v 1.8 knockout (Scn10 -/-) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal-and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy. © 2012 Nature America, Inc. All rights reserved.
Stevenson W.S.,University of Sydney |
Hyland C.D.,Cancer and Haematology Division |
Zhang J.-G.,Cancer and Haematology Division |
Morgan P.O.,Cancer and Haematology Division |
And 18 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010
With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5- ureidoimidazoline decarboxylase inmost vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase, Urah, that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutantencoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking Urah suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.
Ramezani A.,George Washington University |
Dubrovsky L.,George Washington University |
Pushkarsky T.,George Washington University |
Sviridov D.,Baker International Diabetes Institute |
And 4 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2015
Previous studies demonstrated that liver X receptor (LXR) agonists inhibit human immunodeficiency virus (HIV) replication by upregulating cholesterol transporter ATP-binding cassette A1 (ABCA1), suppressing HIV production, and reducing infectivity of produced virions. In this study, we extended these observations by analyzing the effect of the LXR agonist T0901317 [N-[4-(1,1,1,3,3,3-hexafluoro- 2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide] on the ongoing HIV infection and investigating the possibility of using LXR agonist for pre-exposure prophylaxis of HIV infection in a humanized mouse model. Pre-exposure of monocyte-derived macrophages to T0901317 reduced susceptibility of these cells to HIV infection in vitro. This protective effect lasted for up to 4 days after treatment termination and correlated with upregulated expression of ABCA1, reduced abundance of lipid rafts, and reduced fusion of the cellswith HIV. Pre-exposure of peripheral blood leukocytes to T0901317 provided only a shortterm protection against HIV infection. Treatment of HIV-exposed humanized mice with LXR agonist starting 2 weeks postinfection substantially reduced viral load. When eight humanized mice were pretreated with LXR agonist prior to HIV infection, five animals were protected from infection, two had viral load at the limit of detection, and one had viral load significantly reduced relative to mock-treated controls. T0901317 pretreatment also reduced HIVinduced dyslipidemia in infected mice. In conclusion, these results reveal a novel link between LXR stimulation and cell resistance to HIV infection and suggest that LXR agonists may be good candidates for development as anti-HIV agents, in particular for pre-exposure prophylaxis of HIV infection. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
Hansen J.,Copenhagen University |
Brandt C.,Copenhagen University |
Nielsen A.R.,Copenhagen University |
Hojman P.,Copenhagen University |
And 4 more authors.
Endocrinology | Year: 2011
Follistatin is a member of the TGF- super family and inhibits the action of myostatin to regulate skeletal muscle growth. The regulation of follistatin during physical exercise is unclear but may be important because physical activity is a major intervention to prevent age-related sarcopenia. First, healthy subjects performed either bicycle or one-legged knee extensor exercise. Arterial-venous differences were assessed during the one-legged knee extensor experiment. Next, mice performed1hof swimming, and the expression of follistatin was examined in various tissues using quantitative PCR. Western blotting assessed follistatin protein content in the liver. IL-6 and epinephrine were investigated as drivers of follistatin secretion. After 3 h of bicycle exercise, plasma follistatin increased 3 h into recovery with a peak of 7-fold. No net release of follistatin could be detected from the exercising limb. In mice performing a bout of swimming exercise, increases in plasma follistatin as well as follistatin mRNA and protein expression in the liver were observed. IL-6 infusion to healthy young men did not affect the follistatin concentration in the circulation. When mice were stimulated with epinephrine, no increase in the hepatic mRNA of follistatin was observed. This is the first study to demonstrate that plasma follistatin is increased during exercise and most likely originates from the liver. These data introduce new perspectives regarding muscle-liver cross talk during exercise and during recovery from exercise. Copyright © 2010 The Endocrine Society. All rights reserved.