%0 Journal Article %~ PubMed %A Leader, Natasha J %A Ryan, Lynne %A Molyneaux, Lynda %A Yue, Dennis K %T How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes. %B Obesity %D 2013 %C United States %I Wiley-Blackwell Publishing, Inc. %V 21 %N 2 %P 251-253 %@ 1930-739X %X %Z FOR Codes: 699 %0 Journal Article %~ PubMed %A Min, Danqing %A Brooks, Belinda %A Wong, Jencia %A Salomon, Robert %A Bao, Wensheng %A Harrisberg, Brian %A Twigg, Stephen M %A Yue, Dennis K %A McLennan, Susan V %T Alterations in Monocyte CD16 in Association with Diabetes Complications. %B Mediators of Inflammation %D 2012 %C United States %I Hindawi Publishing Corporation %V 2012 %N %P 649083 %@ 1466-1861 %X %Z FOR Codes: 110306 110201 %0 Journal Article %~ PubMed %A Chakera, Ali J %A Carleton, Victoria L %A Ellard, Sian %A Wong, Jencia %A Yue, Dennis K %A Pinner, Jason %A Hattersley, Andrew T %A Ross, Glynis P %T Antenatal diagnosis of fetal genotype determines if maternal hyperglycemia due to a glucokinase mutation requires treatment. %B Diabetes Care %D 2012 %C United States %I American Diabetes Association %V 35 %N 9 %P 1832-1834 %@ 0149-5992 %X %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Simmons, Lisa R %A Molyneaux, Lynda %A Yue, Dennis K %A Chua, Elizabeth L %T Steroid-Induced Diabetes: Is It Just Unmasking of Type 2 Diabetes? %B ISRN Endocrinology %D 2012 %C United States %I Hindawi Publishing Corporation %V 2012 %N %P 910905 %@ 2090-4649 %X Aims. We compared the demographic profile and clinical characteristics of individuals with new onset steroid-induced diabetes (NOSID) to Type 2 diabetes (T2DM) patients with and without steroid treatment. Methods. The demographic profile and clinical characteristics of 60 individuals who developed NOSID were examined and matched to 60 type 2 diabetes patients receiving steroid therapy (T2DM+S) and 360 diabetic patients not on steroids (T2DM) for age, duration of diabetes, HbA1c, gender, and ethnicity. Results. Patients who developed NOSID had less family history of diabetes (P ??? 0.05) and were less overweight (P ??? 0.02). NOSID was more commonly treated with insulin. Despite a matching duration of diabetes and glycaemic control, significantly less retinopathy was found in the group of patients with NOSID (P < 0.03). Conclusions. It appears that steroid treatment primarily precipitated diabetes in a group of individuals otherwise less affected by risk factors of diabetes at that point in time, rather than just opportunistically unmasking preexisting diabetes. Furthermore, the absence of retinopathy suggests that patients with NOSID had not been exposed to long periods of hyperglycaemia. However, the impact of the underlying conditions necessitating steroid treatment and concomitant medications such as immunosuppressants on diabetes development remain to be defined. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Pertot, Tania %A Molyneaux, Lynda %A Tan, Kris %A Ross, Glynis P %A Yue, Dennis K %A Wong, Jencia %T Can We Use Common Clinical Parameters to Identify Patients Who Will Need Insulin Treatment in Gestational Diabetes? %B Diabetes Care %D 2011 %C United States %I American Diabetes Association %V 34 %N 10 %P 2214-22146 %@ 0149-5992 %X To identify patients with gestational diabetes mellitus (GDM) who will need antenatal insulin treatment (AIT) by using a risk-prediction tool based on maternal clinical and biochemical characteristics at diagnosis. %Z FOR Codes: 111402 110306 %0 Journal Article %~ PubMed %A Lo, Lisa %A McLennan, Susan V %A F Williams, Paul %A Bonner, James %A Chowdhury, Sumaiya %A McCaughan, Geoffrey W %A Gorrell, Mark D %A Yue, Dennis K %A Twigg, Stephen M %T Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse obesity model of non-alcoholic steatohepatitis. %B Journal of hepatology %D 2011 %C Netherlands, Denmark %I Elsevier BV %V 55 %N 2 %P 435-44 %@ 0168-8278 %X While type 2 diabetes is an independent risk factor for worsening of human non-alcoholic steatohepatitis (NASH) in clinical studies, it has not been systematically reported in any model whether diabetes exacerbates NASH. The study aim was to determine if diabetes causes NASH progression in a mouse model of diet induced obesity. %Z FOR Codes: 110102 111103 60104 %0 Journal Article %~ PubMed %A Perera, Nimalie Jacintha %A Molyneaux, Lynda %A Constantino, Maria Ines %A McGill, Marg %A Yue, Dennis Koon-See %A Twigg, Stephen Morris %A Ross, Glynis Pauline %T Suboptimal performance of blood glucose meters in an antenatal diabetes clinic. %B Diabetes Care %D 2011 %C United States %I American Diabetes Association %V 34 %N 2 %P 335-337 %@ 0149-5992 %X The objective of this study was to evaluate the performance of blood glucose meters in diabetes associated with pregnancy (DP). %Z FOR Codes: 699 %0 Journal Article %~ PubMed %A Perera, N J %A Stewart, P M %A Williams, P F %A Chua, E L %A Yue, D K %A Twigg, S M %T The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis. %B Diabetic medicine : a journal of the British Diabetic Association %D 2011 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 28 %N 10 %P 1272-6 %@ 1464-5491 %X Icodextrin is a glucose polymer used to maintain an osmotic gradient in peritoneal dialysis. Metabolites of icodextrin are known to cause overestimation of blood glucose in glucose meters using glucose dehydrogenase/pyrroloquinolinequinone systems. The aim of this study is to determine the extent of icodextrin interference in glucose meters using the newer glucose dehydrogenase/NAD or glucose oxidase systems. This has not been established previously. %Z FOR Codes: 1103 %0 Journal Article %A Perera, NJ %A HArding, AJ %A Constantino, MI %A Molyneaux, Lynda %A McGill, Margaret %A Chua, Elizabeth %A Twigg, Stephen %A Ross, GP %A Yue, Dennis %T Triple-B (basal-bolus-booster) subcutaneous insulin regimen: A pragmatic approach to managing hospital inpatient hyperglycaemia %B Practical Diabetes International %D 2011 %C United Kingdom %I John Wiley & Sons Ltd. %V 28 %N 6 %P 266-269 %@ 2047-2900 %X %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Thomson, S E %A McLennan, S V %A Hennessy, A %A Boughton, P %A Bonner, J %A Zoellner, H %A Yue, D K %A Twigg, S M %T A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor. %B Diabetologia %D 2010 %C Germany %I Springer %V 53 %N 3 %P 572-83 %@ 0012-186X %X Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration. %Z FOR Codes: 699 %0 Journal Article %~ PubMed %A Wong, J %A Molyneaux, L %A Constantino, M %A Twigg, S M %A Yue, D K %T Beyond ONTARGET: angiotensin-converting enzyme inhibition and angiotensin II receptor blockade in combination, a lesser evil in some? %B Diabetes, Obesity & Metabolism %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 12 %N 12 %P 1072-1078 %@ 1463-1326 %X Aim: Following the recent Ongoing Telmistartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) finding of adverse renal outcomes, dual renin-angiotensin blockade has fallen out of favour, despite antihypertensive and antiproteinuric efficacy. However, in high-risk severe hypertension, not studied in ONTARGET, whether combination treatment should be withheld or withdrawn is not clear. We examine the renal effects of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) monotherapy versus combination therapy in patients with type 2 diabetes and varying degrees of hypertension. Methods: Subjects attending a hospital diabetes centre were selected as case (combination therapy, n = 120) and control (monotherapy, n = 480). Subjects were matched for age, gender, ethnicity, estimated glomerular filtration rate (eGFR), blood pressure (BP) and study duration. Patients were stratified by BP, hypertension stage 1 (BP < 160/100, n = 506) and stage 2 (???160/100, n = 94), and by treatment group. Data were analysed for the primary renal outcome of eGFR decline ???20 ml/min, over a median of 3.7 years. Results: In keeping with the ONTARGET study, for stage 1 hypertension, combination treatment is significantly worse than monotherapy for the primary outcome of eGFR decline ???20 ml/min (20 vs. 10.7%, p = 0.01). In contrast, for stage 2 hypertension, this endpoint was reached less often for combination versus monotherapy (12.0 vs. 23.2%, p = 0.2). Combination treatment was also not detrimental in patients with proteinuria or eGFR < 60 ml/min and was associated with fewer macrovascular events. Conclusion: Given that hypertension control is paramount and in the spirit of primum non nocere, these data are reassuring should clinicians choose to use ACE-I and ARB combination therapy in the very hypertensive diabetic patient. %Z FOR Codes: 30406 110299 110306 %0 Journal Article %~ PubMed %A Bao, Wensheng %A Min, Danqing %A Twigg, Stephen M %A Shackel, Nicholas %A Warner, Fiona J %A Yue, Dennis K %A McLennan, Susan V %T Monocyte CD147 is induced by Advanced Glycation Endproducts (AGEs) and High Glucose Concentration: Possible role in diabetic complications. %B American journal of physiology. Cell physiology %D 2010 %C United States %I American Physiological Society %V 299 %N 5 %P C1212-9 %@ 1522-1563 %X CD147 is a highly glycosylated transmembrane protein that is known to play a role in regulation of many protein families. It has the unique ability to maintain functional activity in both the membrane bound state and in the soluble form. CD147 is known to play a role in regulation of matrix metalloproteinase (MMP) expression, but whether its expression is affected by the diabetic milieu is not known, and its role in regulation of monocyte MMPs in this environment has not been investigated. Therefore, in this study we investigated the effect of advanced glycation end products (AGEs) and high glucose (HG; 25 mM), on monocyte CD147 expression. Culture of THP-1 monocytes in the presence of AGEs or HG significantly increased CD147 at the gene and protein level. THP-1 cell results were confirmed using freshly isolated monocytes from human volunteers. The effect of AGEs and HG on CD147 expression was also mimicked by addition of proinflammatory cytokines. Addition of AGEs or HG also increased expression of monocyte MMP-1 and MMP-9 but not MMP-2. This increase in MMPs was significantly attenuated by inhibition of CD147 using either a small interfering RNA or an anti-CD147 antibody. Inhibition of NF-??B or addition of antibodies to either TNF-?? or the receptor for AGE (RAGE) each significantly prevented in a dose-dependent manner the induction of CD147 gene and protein by AGE and also decreased MMP-1 and MMP-9. This novel result shows that AGEs can induce monocyte CD147 expression, an effect mediated by inflammatory pathways and RAGE. Because MMPs play a role in monocyte migration, inhibition of their regulator CD147 may assist in the prevention of diabetic complications, particularly those where monocyte infiltration is an early initiating event. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Ban, C R %A Twigg, S M %A Franjic, B %A Brooks, B A %A Celermajer, D %A Yue, D K %A McLennan, S V %T Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction. %B Diabetes Research and Clinical Practice %D 2010 %C Ireland, Belgium %I Elsevier Ireland Ltd %V 87 %N 3 %P 335-341 %@ 0168-8227 %X Circulating matrix metalloproteinase (MMP) levels may correlate with diabetic complications. Whether they are changed in early diabetic cardiomyopathy is not known and was examined in this study. TIMP-1 and collagen degradation products were also measured. Results from subjects with and without diastolic dysfunction were compared with those obtained for patients with varying stages of diabetic renal disease. Patients with type 2 diabetes with or without diastolic dysfunction with varying degrees of renal disease were recruited for this study. Age-matched non-diabetic subjects served as controls. MMPs (-1, -3 and -7) and TIMP-1 were measured by ELISA, MMP-2 and -9 by zymography and collagen degradation products by radioimmunoassay. Differences in the pattern of MMPs/TIMPs and collagen degradation products were observed. The most consistent change was in totalMMP-7, which was increased in those with diastolic dysfunction and those with macroalbuminuria. MMP-7 correlated with cardiac function (p<0.05 vs control, in those with diastolic dysfunction), and renal filtration function (p<0.05 vs control). In summary, we have identified novel relationships between serum MMP-7 and diabetic complications specifically in renal disease and in diastolic dysfunction. How increased circulating MMP-7 is associated with these diabetic microvascular complications and the significance of these findings will require prospective studies. %Z FOR Codes: 1102 1103 601 %0 Journal Article %~ PubMed %A Luo, C %A Wong, J %A Brown, M %A Hooper, M %A Molyneaux, L %A Yue, D K %T Hypovitaminosis D in Chinese type 2 diabetes: lack of impact on clinical metabolic status and biomarkers of cellular inflammation. %B Diabetes and Vascular Disease Research %D 2009 %C United Kingdom %I Sage Publications Ltd. %V 6 %N 3 %P 194-199 %@ 1752-8984 %X OBJECTIVE: Low vitamin D (25 OH vitamin D) is implicated in the development of diabetes and the metabolic syndrome. We examined whether hypovitaminosis D has a clinically significant impact on glycaemia, metabolic status and inflammatory markers in Chinese patients with established type 2 diabetes. METHODS: Characteristics of 109 patients aged over 50 years were stratified by 25 OH vitamin D status. Patients identified as 25 OH vitamin D deficient (or= 0.4 for all) and no association between 25OHVitD and ferritin or hsCRP (p >or= 0.3 for all). Neither BMI nor the metabolic syndrome affected the incremental rise in 25OHVitD levels during supplementation. CONCLUSION: There is no relationship between hypovitaminosis D and metabolic control or inflammatory markers in established type 2 diabetes.This suggests that at least in Chinese populations, the effect of low vitamin D is not clinically significant once diabetes is established. Future 25OHVitD intervention trials should therefore focus on prevention in pre-diabetes. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Liu, Yu %A Min, Danqing %A Bolton, Thyra %A Nubé, Vanessa %A Twigg, Stephen M %A Yue, Dennis K %A McLennan, Susan V %T Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic Foot Ulcers. %B Diabetes care %D 2009 %C United States %I American Diabetes Association %V 32 %N 1 %P 117-9 %@ 0149-5992 %X We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-beta1 (TGF-beta1) with wound healing rate. %Z FOR Codes: 1103 %0 Book Section %A Yue, Dennis %A McGill, Margaret %T Insulin Therapy %B Diabetes in Old Age, 3rd Ed. %D 2009 %C United Kingdom %I Wiley-Blackwell %V %N %P 265-272 %@ 9780470065624 %E Sinclair, Alan J %X %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Overland, J %A Molyneaux, L %A Tewari, S %A Fatouros, R %A Melville, P %A Foote, D %A Wu, T %A Yue, D K %T Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system. %B Diabetes, Obesity and Metabolism %D 2009 %C United Kingdom, Unit %I Wiley-Blackwell Publishing Ltd. %V 11 %N 5 %P 460-463 %@ 1463-1326 %X AIMS: To use continuous glucose monitoring (CGMS) to compare glucose profiles in people with type 1 diabetes following injection of insulin into an area affected by lipohypertrophy vs. an area not affected by lipohypertrophy. METHODS: Eight patients with type 1 diabetes underwent 72 h of CGMS while following a standardized diet and injecting all insulin either into an area with or without lipohypertrophy. Patients underwent two testing periods in random order, separated by 4 days. On day 1 of each test subjects were admitted for measurement of insulin and plasma glucose levels immediately prior to, and hourly for 4 h following, a standardized lunch. RESULTS: Insulin area under the curve (AUC)(0-4 h) was similar for both test periods; 656; interquartile range (IQR): 518-1755 (normal tissue) vs. 602; IQR: 382-1436 (lipohypertrophic tissue), z = 1.7, p = 0.09. There was also no difference in the median time to maximal insulin concentration (Time(max) 2 h; IQR: 2-3 h; z = 0.6; p = 0.6). There was a 37.5% increase in mean plasma glucose levels following a standardized meal; however this was not significant between sites (AUC(0-4 h)t = -1.7; p = 0.1). Moreover, there was no difference in CGMS profiles (AUC(1-72 h)t = -0.9; p = 0.4) across the 72-h monitoring period. Overall the prevalence of hypoglycaemia (CGMS readings < 4 mmol/l) was similar between injection sites (11.6 vs. 10.6%, p = 0.1). CONCLUSION: The pharmacokinetic and pharmacodynamic effect of injecting into lipohypertrophic tissue is small in comparison to the usual clinical variation observed with insulin injections. %Z FOR Codes: 69999 %0 Journal Article %~ PubMed %A Min, Danqing %A Lyons, J Guy %A Bonner, James %A Twigg, Stephen M %A Yue, Dennis K %A McLennan, Susan V %T Mesangial cell-derived factors alter monocyte activation and function through inflammatory pathways: possible pathogenic role in diabetic nephropathy. %B American Journal of Physiology: Renal Physiology %D 2009 %C United States %I American Physiological Society %V 297 %N 5 %P F1229-F1237 %@ 1522-1466 %X Infiltration of macrophages to the kidney is a feature of early diabetic nephropathy. For this to happen monocytes must become activated, migrate from the circulation, and infiltrate the mesangium. This process involves degradation of extracellular matrix, a process mediated by matrix metalloproteinases (MMPs). In the present study we investigate the expression of proinflammatory cytokines TNF-alpha, IL-6, and MMP-9 in glomeruli of control and diabetic rodents and use an in vitro coculture system to examine whether factors secreted by mesangial cells in response to a diabetic milieu can induce monocyte MMP-9 expression and infiltration. After 8 wk of diabetes, the glomerular level of TNF-alpha, IL-6, and macrophage number and colocalization of MMP-9 with macrophage were increased (P < 0.01). Coculture of THP1 monocytes and glomerular mesangial cells in 5 or 25 mM glucose increased MMP-9 (5 mM: 65% and 25 mM: 112%; P < 0.05) and conditioned media degradative activity (5 mM: 30.0% and 25 mM: 33.5%: P < 0.05). These effects were reproduced by addition of mesangial cell conditioned medium to THP1 cells. High glucose (25 mM) increased TNF-alpha, IL-6, and monocyte chemoattractant protein-1 in mesangial cell conditioned medium. These cytokines all increased adhesion and differentiation of THP1 cells (P < 0.05), but only TNF-alpha and IL-6 increased MMP-9 expression (50- and 60-fold, respectively; P < 0.05). Our results show that mesangial cell-secreted factors increase monocyte adhesion, differentiation, MMP expression, and degradative capacity. High glucose could augment these effects by increasing mesangial cell proinflammatory cytokine secretion. This mesangial cell-monocyte interaction may be important in activating monocytes to migrate from the circulation to the kidney in the early stages of diabetic nephropathy. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Wong, J %A McLennan, S %A Molyneaux, L %A Min, D %A Twigg, S %A Yue, D %T Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications. %B Diabetologia %D 2009 %C Germany %I Springer %V 52 %N 9 %P 1953-61 %@ 0012-186X %X We examined whether age of type 2 diabetes onset is related to mitochondrial DNA content in peripheral blood monocytes (PBMCs). %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Cheung, N W %A Yue, D K %A Kotowicz, M A %A Jones, P A %A Flack, J R %T A comparison of diabetes clinics with different emphasis on routine care, complications assessment and shared care. %B Diabetic Medicine %D 2008 %C United Kingdom %I Wiley-Blackwell Publishing %V 25 %N 8 %P 974-978 %@ 0742-3071 %X OBJECTIVE: To compare clinical outcomes of patients attending diabetes clinics with different models of care. METHODS: Diabetes centres which participated in the Australian National Diabetes Information Audit and Benchmarking (ANDIAB) data collection were invited to nominate whether they provided (i) routine diabetes care only (model A), (ii) routine care and structured annual complications screening (model B) or (iii) annual review and complications screening in a system of shared care with general practitioners (model C). De-identified case data were extracted from ANDIAB and outcomes according to the three clinic models were compared. RESULTS: Data on 3052 patients from 18 diabetes centres were analysed. Centres which practised annual complications screening (models B and C) had higher rates of nephropathy and lipid screening and a higher rate of attainment of recommended blood pressure and glycated haemoglobin (HbA(1c)) targets. The implementation of appropriate treatment for patients who had not attained the targets was similar for all three clinic models. CONCLUSIONS: In our study, clinic models which incorporate a system of structured complications screening were more likely to have met screening guidelines. Patients in a shared-care model were at least as likely to have met management targets as those attending diabetes clinics for their routine care. Therefore, a system of shared care by general practitioners supported by annual review at a diabetes clinic may be an acceptable model which improves the capacity to manage large numbers of people with diabetes, without loss of quality of care. %Z FOR Codes: 1117 %0 Journal Article %~ PubMed %A Wong, Jencia %A Nock, Nora L %A Xu, Zhiying %A Kyle, Cam %A Daniels, Andre %A White, Marie %A Yue, Dennis K %A Elston, Robert C %A Mountjoy, Kathleen G %T A polymorphism (D20S32e) close to the human melanocortin receptor 3 is associated with insulin resistance but not the metabolic syndrome. %B Diabetes Research and Clinical Practice %D 2008 %C Ireland %I Elsevier Ireland Ltd %V 80 %N 2 %P 203-207 %@ 0168-8227 %X Insulin resistance (IR) is postulated to underlie diabetes, the metabolic syndrome (MS) and cardiovascular disease (CVD). The D20S32e marker close to the melanocortin receptor-3 (hMC3-R) has been shown to be associated with IR in a large New Zealand M??ori kindred, a population at high risk for MS and CVD. Here we examine the potential association of the D20S32e marker with the MS in this 60 member M??ori kindred. There was a significant association between the D20S32e "B" allele and the fasting insulin component under both polygenic (beta=-5.3077; p=0.008) and common sibship effect (beta=-4.2161; p=0.03) models. No significant association between the same allele of D20S32e and the MS was observed after adjusting for age under a polygenic (p=0.103) or sibling (p=0.09) correlation model. We conclude that in this M??ori kindred, the D20S32e polymorphism is significantly associated with insulin resistance but not with MS. Our data supports the hypothesis that multiple gene variants are necessary for the development of the MS. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Brooks, Belinda A %A McLennan, Susan V %A Twigg, Stephen M %A Yue, Dennis K %T Detection and characterisation of microcirculatory abnormalities in the skin of diabetic patients with microvascular complications. %B Diabetes & Vascular Disease Research %D 2008 %C United Kingdom %I MediNews (Diabetes) Ltd %V 5 %N 1 %P 30-35 %@ 1479-1641 %X The aim of this study was to characterise microvascular blood flow in the skin and to compare it with biomarkers of endothelial dysfunction and tissue inflammation in patients with type 2 diabetes with (n=20) or without (n=20) microvascular complications and 20 control subjects. Microvascular function was measured by laser Doppler velocimetry in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Blood was collected for measurement of biomarkers including plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM) and high-sensitivity C-reactive protein (hsCRP). Both ACh and SNP responses fall progressively with the development of diabetes and microvascular complications. For the total cohort, there was a significant overall correlation between ACh and SNP response (r=0.7, p<0.0001), and this relationship was particularly strong in those with microvascular complications. There was a trend towards higher hsCRP levels across the three groups, but no difference in other biomarkers. Abnormalities of microvascular blood flow are evident in diabetes and become more marked with the development of microvascular complications. This relationship was similar to that shown by the marker of inflammation (hsCRP), but stronger than that pertaining to biomarkers of endothelial function. As both ACh and SNP responses are attenuated, the disturbance is not characteristic of endothelial dysfunction alone. %Z FOR Codes: 110304 110299 %0 Journal Article %~ PubMed %A Sorensen, Lea %A Siddall, Philip J %A Trenell, Michael I %A Yue, Dennis K %T Differences in metabolites in pain-processing brain regions in patients with diabetes and painful neuropathy. %B Diabetes Care %D 2008 %C United States %I American Diabetes Association %V 31 %N 5 %P 980-981 %@ 0149-5992 %X OBJECTIVE: Magnetic resonance spectroscopy (MRS) (specifically, (1)H-MRS) has been used to show changes in the brain following peripheral nerve injury in subjects without diabetes. This study used (1)H-MRS to examine the brain in subjects with or without painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: Twenty-six diabetic subjects (12 with and 14 without chronic neuropathic pain) were compared, with 18 subjects without diabetes and pain. The left thalamus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) were assessed using (1)H-MRS. RESULTS: In the DLPFC, diabetic subjects had a decrease in N-acetyl aspartate (NAA) and creatine relative to the control group. In the thalamus, there was a reduction of NAA in the diabetic group with pain compared with that in patients with diabetes and no pain. CONCLUSION: Subjects with diabetes have metabolite differences in the brain compared with control subjects. Subjects with painful neuropathy showed reduced NAA in the thalamus, which may explain the genesis of pain in some cases. %Z FOR Codes: 110306 1109 %0 Journal Article %~ PubMed %A Wong, Jencia %A Molyneaux, Lynda %A Zhao, Deming %A Constantino, Maria %A Gray, Robert S %A Twigg, Stephen M %A Xu, Zhang Rong %A Yue, Dennis K %T Different accelerators to early-onset Type 2 diabetes: a comparison of Anglo-Celtic and Chinese patients. %B Journal of diabetes and its complications %D 2008 %C United States %I Elsevier %V 22 %N 6 %P 389-94 %@ 1056-8727 %X The "accelerator hypothesis" postulates that metabolic syndrome (MS) factors-overweight and insulin resistance-increase functional demand on islets, accelerating diabetes onset to a younger age in both Type 1 and Type 2 diabetes (T2DM). Previous research has focused only on the former. We examine to what extent the MS and individual components are accelerators to the earlier onset of T2DM in Anglo-Celtic and Chinese populations. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Brooks, Belinda %A Delaney-Robinson, Carol %A Molyneaux, Lynda %A Yue, Dennis K %T Endothelial and neural regulation of skin microvascular blood flow in patients with diabetic peripheral neuropathy: effect of treatment with the isoform-specific protein kinase C beta inhibitor, ruboxistaurin. %B Journal of diabetes and its complications %D 2008 %C United States %I Elsevier Inc. %V 22 %N 2 %P 88-95 %@ 1056-8727 %X PURPOSE: This article aims to study the effects of ruboxistaurin (RBX) on skin microvascular blood flow (SkBF) and evaluate the relationship between endothelial and neural control of SkBF in patients with diabetic peripheral neuropathy (DPN). METHODS: We studied 11 placebo- and 9 RBX (32 mg/day)-treated patients who participated in a 1-year, double-masked, randomized, Phase 3 study of RBX for treatment of DPN sensory symptoms. Patients had type 1 or type 2 diabetes, a detectable sural sensory nerve action potential, and Neuropathy Total Symptom Score-6 (NTSS-6) >6 points. SkBF was measured by laser Doppler velocimetry, combined with iontophoresis of acetylcholine and sodium nitroprusside, at baseline, 3 months, and 1 year. Sensory symptoms and electrophysiology were also evaluated during the study. The relationship between endothelial and neural control of SkBF at baseline was assessed using linear regression. RESULTS: No significant differences (RBX vs. placebo) were demonstrable for post-iontophoresis SkBF [fold increase from basal state (1 year): endothelium-dependent, 3.6 vs. 8.6; endothelium-independent, 3.7 vs. 2.0; C fiber-mediated, 1.7 vs. 2.0; P>.05] or sensory symptoms [NTSS-6 total score (1 year): 7.7 vs. 6.0 points; P=.4]. There were also no significant between-group differences in nerve conduction parameters, except for placebo peroneal nerve conduction velocity, which demonstrated a statistically significant improvement of unknown clinical importance (Z=2.1; P=.034). At baseline, C fiber-mediated vasodilatation correlated well with endothelium-dependent vasodilation (r=.7, P<.01) but not with endothelium-independent vasodilatation (r=-.1, P=.7). CONCLUSIONS: RBX demonstrated no effect on SkBF or sensory symptoms after 1 year in this cohort. The correlation between C fiber-mediated and endothelium-dependent SkBF at baseline suggests that improving endothelial function could affect the microcirculation not only locally but also via the neurovascular arcade. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Thomson, Sally E %A McLennan, Susan V %A Kirwan, Paul D %A Heffernan, Scott J %A Hennessy, Annemarie %A Yue, Dennis K %A Twigg, Stephen M %T Renal connective tissue growth factor correlates with glomerular basement membrane thickness and prospective albuminuria in a non-human primate model of diabetes: possible predictive marker for incipient diabetic nephropathy. %B Journal of diabetes and its complications %D 2008 %C United States %I Elsevier Inc. %V 22 %N 4 %P 284-94 %@ 1056-8727 %X Diabetic renal disease is characterized by accumulation of extracellular matrix, glomerulosclerosis, and tubulointerstitial fibrosis. Connective tissue growth factor (CTGF) is implicated in these changes, as it contributes to new matrix synthesis and is increased in the diabetic kidney. CTGF also inhibits mesangial matrix degradation through up-regulation of the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). In a non-human primate model of diabetes, we determined whether the level of renal CTGF protein before development of albuminuria correlated with renal matrix and TIMP-1 changes and whether renal CTGF predicts progression to albuminuria. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A McLennan, Susan V %A Bonner, James %A Milne, Sgtephen %A Lo, Lisa %A Charlton, Ana %A Kurup, Savita %A Jia, Junhong %A Yue, Dennis K %A Twigg, Stephen M %T The anti-inflammatory agent Propolis improves wound healing in a rodent model of experimental diabetes. %B Wound Repair and Regeneration %D 2008 %C United States %I Wiley-Blackwell %V 16 %N 5 %P 706-713 %@ 1524-475X %X Foot ulcers and poor wound healing are problematic for patients with diabetes. The beehive protectant Propolis can improve wound healing but whether it can improve healing in diabetic wounds has not been investigated. In this study, the effect of a single application of Propolis on epithelial closure, wound morphology, cellular infiltrate, and blood vessel density were investigated. Diabetes was induced in rats using streptozocin. After 6 weeks, diabetic and control animals were wounded and the wounds were treated with Propolis or saline as control. At days 6 and 12 animals were sacrificed and wounds were excised. Compared with controls, diabetes decreased epithelial closure and reepithelialization but had no effect on wound contraction. These delays were prevented by Propolis. At day 12, the impaired macrophage infiltration (C:1.49+/-0.09 vs. D:0.25+/-0.14), persistent neutrophil infiltration (C:0.22+/-0.19 vs. D:1.33+/-0.81), and increased myeloperoxidase activity (fourfold) in diabetic wounds were prevented by Propolis. Diabetes had no effect on wound volume, vessel number, or branch points. These novel data indicate that Propolis can accelerate wound healing in diabetes. As neutrophil infiltration is normalized, its mechanism of action may be through anti-inflammatory pathways. This result and the established safety profile of Propolis provide a rationale for studying topical application of this agent in a clinical setting. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Brooks, Belinda A %A Heffernan, Scott %A Thomson, Sally %A McLennan, Susan V %A Twigg, Stephen M %A Yue, Dennis K %T The effects of diabetes and aminoguanidine treatment on endothelial function in a primate model of type 1 diabetes. %B American journal of primatology %D 2008 %C United States %I John Wiley & Sons, Inc. %V 70 %N 8 %P 796-802 %@ 1098-2345 %X Abnormalities of endothelial function have been demonstrated in diabetes and are thought to play a role in the pathogenesis of diabetic complications. The aims of this study were to determine whether aminoguanidine, an inhibitor of glycation, can prevent endothelial and microcirculation abnormalities in a primate model of type 1 diabetes. Male baboons (Papio hamadryas) were assigned to one of the four groups: control, diabetes, control treated with aminoguanidine or diabetes treated with aminoguanidine. Diabetes was induced by streptozocin (60 mg/kg) and treated with once daily injection of insulin. Aminoguanidine was given subcutaneously (10 mg/kg), once a day. Diabetic animals had a mean duration of diabetes of 8.9 +/- 3.4 years and HbA1c of 8.9 +/- 1.1%. Microvascular function was measured by laser Doppler velocimetry, with examination of endothelium-dependent increase in skin blood flow (SkBF) following iontophoresis of acetylcholine (ACh) and endothelium-independent increase in SkBF in response to the nitric oxide (NO) donor sodium nitroprusside (SNP). Multiple regression analysis identified diabetes (P = 0.049) and aminioguanidine treatment (P = 0.026) as significant determinants of ACh response. The diabetic baboons treated with aminoguanidine had less Ach-mediated SkBF response compared with controls (1.39 +/- 0.32 vs. 2.26 +/- 0.61, F = 3.3, P = 0.04), but there was no difference between groups in SkBF response to SNP. We conclude that endothelial dysfunction can be demonstrated in this primate model of type 1 diabetes at a stage when overt diabetic complications are not present. This occurred in the absence of insulin resistance or significant hypercholesterolemia. Administration of aminoguanidine from the onset of diabetes was not able to prevent this abnormality and in fact aggravated the endothelial response. Effects of aminoguanidine on NO synthase may contribute to this phenomenon. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Jiang, L %A Wang, A %A Molyneaux, L M %A Constantino, M I %A Yue, D K %T The long-term impact of ferritin level on treatment and complications of type 2 diabetes. %B Diabetes, obesity & metabolism %D 2008 %C United Kingdom %I Wiley-Blackwell %V 10 %N 6 %P 519-522 %@ 1463-1326 %X AIM: To investigate if high-serum ferritin has long-term impact on response to treatment and the development of diabetic complications in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We analysed the record of 90 consecutive type 2 diabetic subjects who had serum ferritin level determined soon after diagnosis of diabetes and who also had long-term follow-up data. RESULTS: Patients with higher serum ferritin level had slightly worse triglyceride, blood pressure and liver enzyme levels at the end of follow up. However, ferritin level had no impact on the initial or final requirements for diabetic medication and the development of diabetic complications. CONCLUSIONS: Although elevated serum ferritin is a marker of insulin resistance and chronic inflammation, it is not necessarily a bad prognostic indicator that should affect the clinician''s approach to management. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A McGill, Margaret %A Molyneaux, Lynda %A Twigg, Stephen M %A Yue, Dennis K %T The metabolic syndrome in type 1 diabetes: does it exist and does it matter? %B Journal of Diabetes and its Complications %D 2008 %C USA %I Elsevier %V 22 %N 1 %P 18-23 %@ 1056-8727 %X The significance of the metabolic syndrome in type 1 diabetes is not well understood. This study aimed to estimate its prevalence and attendant complications. Four hundred twenty-seven type 1 diabetic subjects were grouped according to the presence or absence of metabolic syndrome (WHO criteria). Macro- and microvascular complications were compared between the groups as individual and as composite endpoints. Data were analyzed for the total cohort and in subgroups according to duration of diabetes quartiles (<6.9, 7-12.9, 13-19.9, and >20 years) and year of presentation. Fifteen percent of individuals fulfilled the WHO criteria for metabolic syndrome, and of these, 26.9% were insulin resistant, as compared with 3.4% of those without metabolic syndrome [odds ratio (OR)=8.9, P=.001]. Both BMI and metabolic syndrome showed an increasing trend from 1992 to 2003. Those with metabolic syndrome required significantly higher insulin dosage [0.9 (0.7-1.2) vs. 0.6 (0.5-0.9) units/kg, P=.03], were older [35.0 (26.2-47.3) vs. 29.7 (23.4-36.4) years, P=.002], and had longer duration of diabetes [19.7 (10.7-25.6) vs. 12.1 (6.3-17.9) years, P=.0001]. They also had a significantly higher macrovascular composite endpoint (OR=3.3, P=.02) as well as higher macrovascular and microvascular composite endpoint (OR=3.1, P=.0001). The prevalence of stroke (OR=22.8, P=.008), peripheral vascular disease (OR=7.3, P=.05), and severe retinopathy (OR=3.7, P=.01) is higher in subjects with metabolic syndrome in the >or=20-year quartile group; in addition, these subjects have higher macrovascular composite endpoint (OR=3.9, P=.03) and macrovascular and microvascular composite endpoint (OR=2.9, P=.03). This remained so even when subjects with albuminuria were excluded. Some individuals with type 1 diabetes can also have metabolic syndrome. They are more prone to complications and require even more intensive glycemic control and reduction of macrovascular risk factors. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Wong, Jencia %A Molyneaux, Lynda %A Constantino, Maria %A Twigg, Stephen M %A Yue, Dennis K %T Timing is Everything: Age of Onset Influences Long Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors. %B Diabetes care %D 2008 %C United States %I American Diabetes Association %V 31 %N 10 %P 1985-90 %@ 0149-5992 %X To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A McLennan, S V %A Kelly, D J %A Schache, M %A Waltham, M %A Dy, V %A Langham, R G %A Yue, D K %A Gilbert, R E %T Advanced glycation end products decrease mesangial cell MMP-7: A role in matrix accumulation in diabetic nephropathy? %B Kidney international %D 2007 %C United States %I Nature Publishing Group %V 72 %N %P 481-8 %@ 1523-1755 %X Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-beta. %Z FOR Codes: %0 Journal Article %~ PubMed %A Xu, Ling %A McLennan, Susan V %A Lo, Lisa %A Natfaji, Anas %A Bolton, Thyra %A Liu, Yu %A Twigg, Stephen M %A Yue, Dennis K %T Bacterial load predicts healing rate in neuropathic diabetic foot ulcers. %B Diabetes care %D 2007 %C 1701 N BEAUREGARD ST %I Amer Diabetes Assoc %V 30 %N 2 %P 378-380 %@ 0149-5992 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Brooks, B A %A Franjic, B %A Ban, C R %A Swaraj, K %A Yue, D K %A Celermajer, D S %A Twigg, S M %T Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes. %B Diabetes, obesity & metabolism %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 10 %N 0 %P 739-46 %@ 1462-8902 %X Diabetic cardiomyopathy is an increasingly recognized entity. The pathogenic factors that may contribute to its development, especially the earliest changes of diastolic dysfunction (DD), have not been clearly defined. Microvessel dysfunction and upregulation of profibrotic growth factors have been described as possible causes. The aim of this study was therefore to determine whether microvascular dysfunction and/or upregulation of the profibrotic connective tissue growth factor (CTGF) are associated with subclinical DD in subjects with type 2 diabetes. %Z FOR Codes: %0 Journal Article %~ Isi %A Zoellner, I %A Twigg, SM %A Yue, DK %A Bonner, J %A Hennessy, A %A Thomson, SE %A McLennan, SV %T Dysregulated inflammation predicts reduced connective tissue growth factor expression in a baboon wound healing model of type 1 diabetes %B Diabetologia %D 2007 %C Germany %I Springer-Verlag %V 50 %N %P S490-S491 %@ 0012-186X %X %Z FOR Codes: %0 Journal Article %A McLennan, Susan %A McGill, Margaret %A Twigg, Stephen %A Yue, Dennis %T Improving wound-healing outcomes in diabetic foot ulcers %B Expert Review of Endocrinology and Metabolism %D 2007 %C United Kingdom %I Future Drugs %V 2 %N %P 205-213 %@ 1744-6651 %X %Z FOR Codes: 110306 110306 %0 Journal Article %~ PubMed %A McElduff, Aidan %A Yue, Dennis K %T Inhaled insulin: where are we and where might we go? %B The Medical journal of Australia %D 2007 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 186 %N 8 %P 390-391 %@ 1326-5377 %X %Z FOR Codes: %0 Journal Article %A Nubé, Vanessa L %A Bolton, Thyra M %A Chua, Elizabeth %A Yue, Dennis %T Osteomyelitis in the Diabetic Foot: What Lies Beneath. %B Primary Intention %D 2007 %C Australia %I Cambridge Publishing %V 15 %N 2 %P 49-57 %@ 1837-6304 %X %Z FOR Codes: 110306