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Aims: To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support., Methods: Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation., Results: Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002)., Conclusions: Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims/hypothesis: In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses., Methods: Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex., Results: Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p < 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p < 0.001), independent of menopausal status and statin uptake. Adjusted for covariates, fenofibrate reduced total cardiovascular outcomes (cardiovascular death, fatal and non-fatal stroke and carotid and coronary revascularisation) by 30% in women (95% CI 8%, 46%; p = 0.008) and 13% in men (95% CI -1%, 24%; p = 0.07) with no treatment-by-sex interaction (p > 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p > 0.1)., Conclusions/interpretation: Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.

OBJECTIVE The Australian lifestyle intervention program Life! is only the second reported, large-scale diabetes prevention program. This article describes the genesis and the successful establishment of Life! and its key outcomes for participants and implementation. RESEARCH DESIGN AND METHODS Life!, a behavior-change intervention, comprises six group sessions over 8 months. The Victorian Department of Health funded Diabetes Australia-Victoria to implement the program. Experience of the Greater Green Triangle diabetes prevention implementation trial was used for intervention design, workforce development, training, and infrastructure. Clinical and anthropometric data from participants, used for program evaluation, were recorded on a central database. RESULTS Life! has a statewide workforce of 302 trained facilitators within 137 organizations. Over 29,000 Victorians showed interest in Life!, and 15,000 individuals have been referred to the program. In total, 8,412 participants commenced a Life! program between October 2007 and June 2011, and 37% of the original participants completed the 8-month program. Participants completing sessions 1 to 5 lost an average of 1.4 kg weight (P < 0.001) and waist circumference of 2.5 cm (P < 0.001). Those completing six sessions lost an average of 2.4 kg weight (P < 0.001) and waist circumference of 3.8 cm (P < 0.001). The weight loss of 2.4 kg represents 2.7% of participants' starting body weight. CONCLUSIONS The impact of Life! is attributable to applying available evidence for the system's design of the intervention and collaboration between policy makers, implementers, and evaluators using the principles of continuous quality improvement to support successful, large-scale recruitment and implementation.

Background: To compare and contrast the coronary heart disease (CHD) risk factors of lower socio-economic status public hospital patients with those of privately insured CHD patients before and after six months of telephone delivered coaching using The COACH Program., Methods: A retrospective observational study which contrasts the lifestyle and biomedical coronary risk factor status of 2256 public hospital patients with the same risk factors of 3278 patients who had private health insurance. All patients received an average of 5 coach sessions over 6 months., Results: The public hospital patients were four years younger and had multiple measures confirming their lower socio-economic status than their private hospital counterparts. At entry to the program, the public hospital patients had worse risk factor levels than the privately insured patients for total and LDL-cholesterol, triglycerides, fasting glucose, smoking and physical activity levels (P<0.0001) but better status for systolic and diastolic blood pressures and alcohol intake. At exit from the program, many of these differences had diminished or disappeared. The public hospital patients had greater improvements in their risk factor status for total and LDL-cholesterol, fasting glucose, body weight, smoking status and physical activity level than did the privately insured patients (P<0.05)., Conclusions: This paper demonstrates that a program of initiating contact with patients with CHD, identifying treatment gaps in their management and coaching to achieve guideline recommended risk factor targets can help reduce health inequalities in such patients and thus benefit all patients in the context of ongoing secondary prevention., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the effectiveness of goal focused telephone coaching by practice nurses in improving glycaemic control in patients with type 2 diabetes in Australia., Design: Prospective, cluster randomised controlled trial, with general practices as the unit of randomisation., Setting: General practices in Victoria, Australia., Participants: 59 of 69 general practices that agreed to participate recruited sufficient patients and were randomised. Of 829 patients with type 2 diabetes (glycated haemoglobin (HbA1c) >7.5% in the past 12 months) who were assessed for eligibility, 473 (236 from 30 intervention practices and 237 from 29 control practices) agreed to participate., Intervention: Practice nurses from intervention practices received two days of training in a telephone coaching programme, which aimed to deliver eight telephone and one face to face coaching episodes per patient., Main Outcome Measures: The primary end point was mean absolute change in HbA1c between baseline and 18 months in the intervention group compared with the control group., Results: The intervention and control patients were similar at baseline. None of the practices dropped out over the study period; however, patient attrition rates were 5% in each group (11/236 and 11/237 in the intervention and control group, respectively). The median number of coaching sessions received by the 236 intervention patients was 3 (interquartile range 1-5), of which 25% (58/236) did not receive any coaching sessions. At 18 months' follow-up the effect on glycaemic control did not differ significantly (mean difference 0.02, 95% confidence interval -0.20 to 0.24, P=0.84) between the intervention and control groups, adjusted for HbA1c measured at baseline and the clustering. Other biochemical and clinical outcomes were similar in both groups., Conclusions: A practice nurse led telephone coaching intervention implemented in the real world primary care setting produced comparable outcomes to usual primary care in Australia. The addition of a goal focused coaching role onto the ongoing generalist role of a practice nurse without prescribing rights was found to be ineffective., Trial Registration: Current Controlled Trials ISRCTN50662837.

Introduction: For Aboriginal populations, predicting individuals at risk of cardiovascular disease (CVD) is difficult due to limitations and inaccuracy in existing risk-prediction algorithms. We examined conventional and novel risk factors associated with insulin resistance and the metabolic syndrome and assessed their relationships with subsequent CVD events., Design: Longitudinal cohort., Methods: Aboriginal people (n = 739) from Central Australia completed population-based risk-factor surveys in 1995 and were followed up in 2005. Principal components analysis (PCA), regression and univariate analyses (using ROC defined cut-off points) were used to identify useful clinical predictors of primary CVD., Results: PCA yielded five components: (1) lipids and liver function; (2) insulin resistance; (3) blood pressure and kidney function; (4) glucose tolerance; and (5) anti-inflammatory (low fibrinogen, high HDL cholesterol). Components 2, 3 and 4, and age were significant independent predictors of incident CVD, and smoking approached significance. In univariate analysis fasting glucose ≥ 4.8 mmol/l, total:HDL cholesterol ratio ≥ 5.7, non-HDL cholesterol ≥ 4.3 mmol/l, gamma-glutamyl transferase ≥ 70 U/l, albumin creatinine ratio ≥ 5.7 mg/mmol, systolic blood pressure ≥ 120 mmHg and diastolic blood pressure ≥ 70 mmHg were useful predictors of CVD. The co-occurrence of three or more risk variables (fasting glucose ≥ 4.8 mmol/l, total:HDL cholesterol ratio ≥ 5.7, blood pressure (systolic ≥ 120 mmHg; diastolic ≥ 70 mmHg; albumin:creatinine ratio ≥ 5.7 mg/mmol and smoking) had sensitivity of 82.0% and specificity of 59.9% for predicting incident CVD., Conclusion: Age is the strongest predictor of CVD for this population. For clinical identification of individuals at high risk, screening for the combination of three or more of hyperglycaemia, dyslipidaemia, hypertension, albuminuria and smoking may prove a useful and efficient strategy.

Background: The successful Greater Green Triangle Diabetes Prevention Program (GGT DPP), a small implementation trial, has been scaled-up to the Victorian state-wide 'Life!' programme with over 10,000 individuals enrolled. The Melbourne Diabetes Prevention Study (MDPS) is an evaluation of the translation from the GGT DPP to the Life! programme. We report results from the preliminary phase (pMDPS) of this evaluation., Methods: The pMDPS is a randomised controlled trial with 92 individuals aged 50 to 75 at high risk of developing type 2 diabetes randomised to Life! or usual care. Intervention consisted of six structured 90-minute group sessions: five fortnightly sessions and the final session at 8 months. Participants underwent anthropometric and laboratory tests at baseline and 12 months, and provided self-reported psychosocial, dietary, and physical activity measures. Intervention group participants additionally underwent these tests at 3 months. Paired t tests were used to analyse within-group changes over time. Chi-square tests were used to analyse differences between groups in goals met at 12 months. Differences between groups for changes over time were tested with generalised estimating equations and analysis of covariance., Results: Intervention participants significantly improved at 12 months in mean body mass index (-0.98 kg/m(2), standard error (SE) = 0.26), weight (-2.65 kg, SE = 0.72), waist circumference (-7.45 cm, SE = 1.15), and systolic blood pressure (-3.18 mmHg, SE = 1.26), increased high-density lipoprotein-cholesterol (0.07 mmol/l, SE = 0.03), reduced energy from total (-2.00%, SE = 0.78) and saturated fat (-1.54%, SE = 0.41), and increased fibre intake (1.98 g/1,000 kcal energy, SE = 0.47). In controls, oral glucose at 2 hours deteriorated (0.59 mmol/l, SE = 0.27). Only waist circumference reduced significantly (-4.02 cm, SE = 0.95).Intervention participants significantly outperformed controls over 12 months for body mass index and fibre intake. After baseline adjustment, they also showed greater weight loss and reduced saturated fat versus total energy intake.At least 5% weight loss was achieved by 32% of intervention participants versus 0% controls., Conclusions: pMDPS results indicate that scaling-up from implementation trial to state-wide programme is possible. The system design for Life! was fit for purpose of scaling-up from efficacy to effectiveness., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12609000507280.

Objective: Glycemic control in type 2 diabetes generally worsens over time, requiring intensification of therapy. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial provided the opportunity to observe glycemic control in a real-world setting. We assessed the adequacy of metformin, sulfonylureas, and insulin to maintain glycemic control and their effects on weight., Research Design and Methods: Diabetes control was measured at baseline and yearly for a median of 5 years in the 4,900 patients from the nonintervention arm of this study allocated to placebo., Results: Median HbA(1c) was 6.9% at baseline and increased by an average of 0.22% over 5 years (P < 0.001). Median weight was 86.3 kg at baseline and decreased by 0.4 kg over 5 years (P = 0.002). Baseline therapy was lifestyle measures only in 27%, oral agents without insulin in 59%, and insulin in 14% (7% also taking oral agents). Over 5 years, insulin use increased to 32% (21% also taking oral agents). Use of oral agents remained similar at 56%. Only 2% of patients at baseline and 4% after 5 years were taking oral agents other than metformin or sulfonylureas. Initiation of insulin therapy in 855 patients produced a sustained reduction of HbA(1c) from a median of 8.2 to 7.7%, with a weight gain of 4.6 kg over 5 years., Conclusions: With intensification of traditional therapies, glycemic control deteriorated very little over 5 years in a large cohort of type 2 diabetes. However, the requirement for insulin therapy doubled, at the expense of significant weight gain and risk of hypoglycemia.

Objective: To evaluate an algorithm guiding responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetic patients using real-time continuous glucose monitoring (RT-CGM)., Research Design and Methods: Sixty CSII-treated type 1 diabetic participants (aged 13-70 years, including adult and adolescent subgroups, with A1C

Purpose: To assess whether The COACH Program could sustain its favourable impact on coronary risk factors (CRFs) and adherence to recommended medication for 18 months after the completion of The COACH Program., Method: A clinical audit of a secondary prevention program performed in three teaching hospitals in Melbourne, Victoria for patients with coronary heart disease (CHD). The CRF targets were based on recommendations from the National Heart Foundation of Australia between 2003 and 2007., Results: 656 patients were followed by telephone every 6 months from recruitment in hospital for 2 years. There was a substantial improvement in all CRF from discharge from hospital to the completion of active coaching 6 months after hospital discharge. There was also a significant increase in the proportion of patients taking statins and renin-angiotensin system antagonists in the same period of time. There was a small deterioration in CRF status in the 6 months after exit from The COACH Program but thereafter CRF status was maintained and substantially better than that on entry to The COACH Program. The use of the recommended cardio-protective medications remained at the levels achieved at exit from The COACH Program., Conclusion: The changes in CRF status and adherence to cardiac medications achieved at 6 months in The COACH Program are sustained for at least 18 months after cessation of The COACH Program.

Objective: To describe the processes and costs of engaging practice nurses (PNs) to establish a cluster randomised controlled trial (RCT) to study type 2 diabetes in general practice., Design, Setting and Participants: Descriptive study of the processes and costs of engaging PNs from 59 general practices in Victoria that were participating in the Patient Engagement And Coaching for Health (PEACH) study, prior to practices being randomly assigned in the cluster RCT., Main Outcome Measures: Estimated direct research costs and personnel costs for establishing a general practice-based research project involving PNs (eg, costs for approaching Victorian Divisions of General Practice and the Australian Practice Nurses Association; practice and patient recruitment; research project establishment at general practices; and PNs' training, support and engagement during the study establishment period)., Results: The estimated cost to establish our PN-led general practice-based cluster RCT was over $110 000, with an average cost of $2000 per practice. Direct research and personnel costs were considerably higher than anticipated. Lack of research skills among PNs required intensive hands-on support from the research team., Conclusions: It is feasible to undertake a PN-led, general practice-based clinical trial in diabetes care. Future research funding needs to account for recruitment costs, including the need to build PN research capacity, and to overcome the inherent difficulties of engaging practices in complex intervention trials in primary care., Trial Registration: International Standard Randomised Controlled Trial Number Register ISRCTN50662837.

Background: Amputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems. Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes., Methods: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50-75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation-a prespecified tertiary endpoint of the study-was routinely gathered. Clinicians who were masked to treatment allocation adjudicated amputations as minor or major (below or above the ankle, respectively). Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb, to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease. Analysis was by intention to treat (ITT). The FIELD study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481., Findings: All 9795 patients were included in the ITT population. 115 patients had one or more non-traumatic lower-limb amputations due to diabetes. Previous cardiovascular disease, microvascular disease, previous non-traumatic amputation or skin ulcer, smoking, and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event (all p<0.001 for three-way comparison). Mean lipid concentrations differed between patients who had on-study amputations and those who had other cardiovascular events or neither event, but by no more than 0.2 mmol/L. The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0.64, 95% CI 0.44-0.94; p=0.02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0.53, 0.30-0.94; p=0.027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0.93, 0.53-1.62; p=0.79)., Interpretation: Classic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes. Treatment with fenofibrate was associated with a lower risk of amputations, particularly minor amputations without known large-vessel disease, probably through non-lipid mechanisms. These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations., Funding: Laboratoires Fournier SA (now part of Solvay Pharmaceuticals) and National Health and Medical Research Council of Australia.

Objective: To evaluate the extent to which the current Pharmaceutical Benefits Scheme (PBS) guidelines for patient eligibility for lipid-lowering medication are applicable to Aboriginal people in Central Australia., Design, Setting and Participants: A 10-year cohort study of 659 Aboriginal people who participated in population-based cardiovascular disease (CVD) risk factor surveys in 1995 and who were free of CVD at baseline, for the period from 1995 to 2004-2005 or until first CVD event. Evidence of atherosclerotic CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) was sought from hospital, primary health care and death records. PBS eligibility was assigned according to the current PBS criteria, which were amended in 2006 to include Aboriginal-specific criteria, using participants' baseline (1995) and 10-year follow-up data., Main Outcome Measures: Proportions of PBS-eligible and PBS-ineligible participants who had CVD events during the study period; sensitivity and specificity of the criteria., Results: Of 42 participants who had CVD events during the study period, 35 were PBS-eligible (incidence, 1130/100 000 person-years; relative risk compared with PBS-ineligible population, 4.87 [95% CI, 2.19-10.80]) and seven were PBS-ineligible. PBS eligibility was associated with older mean age (37 v 32 years) and male sex (48% v 37%), with 50.7% of participants (334/659) meeting eligibility criteria. The mean high-density lipoprotein cholesterol level at baseline was very low in both groups (0.81 v 0.87 mmol/L). The current PBS guidelines have low specificity (52%) in this population, which was found to improve (to 71%-82%) by incorporating additional non-lipid criteria (age and multiple non-lipid risk factors)., Conclusion: The current PBS lipid treatment criteria, which include any Aboriginal person with diabetes and less stringent cholesterol thresholds than the previous version, identify a group at very high risk of CVD. Global risk assessment may better identify those at risk.

Aim: To determine if levels of coated-platelets, which are potentially pro-thrombotic, are increased in end-stage renal disease patients on haemodialysis, a condition associated with high cardiovascular disease risk., Methods: In a cross-sectional observational study, coated-platelet levels were measured by flow cytometry in 25 end-stage renal failure haemodialysis patients and 25 controls without renal disease. Associations between coated-platelet levels and clinical and biochemical factors relevant to renal and cardiovascular disease were evaluated., Results: Mean +/- SD coated-platelet levels were higher in the dialysis group than in the control group (39.3+/-14.3% vs 30.9+/-10.3%, P=0.02). The number of subjects with high coated-platelet levels (>40%) was larger in the dialysis than in the control group (13/25 vs 4/25, chi(2) test, P=0.007). On univariate analysis, coated-platelet levels correlated with serum C-reactive protein levels in renal failure (r=0.47, P=0.02) and inversely with white cell count in the control group (r= -0.60, P=0.001). Coated-platelet levels were higher in dialysis patients reporting alcohol abstinence than among those reporting 'social' drinking (44.3+/-12.6 vs 28.8+/-13.5%, P=0.01). Age, gender, body weight, smoking, diabetes, lipid levels and lipid-lowering drugs were not associated with coated-platelet levels (all P>0.05)., Conclusion: Coated-platelet levels are increased in haemodialysis patients relative to subjects with normal renal function, and are related to inflammation and alcohol abstinence. Other vascular risk factors, such as smoking, lipids and diabetes, were not related to coated-platelet levels. Coated-platelets may be implicated in the increased thrombosis and vascular risk in end-stage renal disease.

Objective: There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components., Research Design and Methods: Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004-2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25-84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure., Results: Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12-3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76-3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06-3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression., Conclusions: Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.

Objective: To examine mortality from all causes and from cardiovascular disease (CVD), and CVD hospitalisation rate for a decentralised Aboriginal community in the Northern Territory., Design and Participants: For a community-based cohort of 296 people aged 15 years or older screened in 1995, we reviewed hospital and primary health care records and death certificates for the period up to December 2004 (2800 person-years of follow-up)., Main Outcome Measures: Mortality from all causes and CVD, and hospitalisation with CVD coded as a primary cause of admission; comparison with prior trends (1988 to 1995) in CVD risk factor prevalence for the community, and with NT-specific Indigenous mortality and hospitalisation rates., Results: Mortality in the cohort was 964/100,000 person-years, significantly lower than that of the NT Indigenous population (standardised mortality ratio [SMR], 0.62; 95% CI, 0.42-0.89). CVD mortality was 358/100,000 person-years for people aged 25 years or older (SMR, 0.52; 95% CI, 0.23-1.02). Hospitalisation with CVD as a primary cause was 13/1000 person-years for the cohort, compared with 33/1000 person-years for the NT Indigenous population., Conclusion: Contributors to lower than expected morbidity and mortality are likely to include the nature of primary health care services, which provide regular outreach to outstation communities, as well as the decentralised mode of outstation living (with its attendant benefits for physical activity, diet and limited access to alcohol), and social factors, including connectedness to culture, family and land, and opportunities for self-determination.

Objectives: Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients., Methods: Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects., Results: Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance)., Conclusions: LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

Aim: To investigate the effect of a thiazolidinedione on proteinuria in patients with non-diabetic renal disease., Methods: In an open-label randomized cross-over study, 40 adults with chronic non-diabetic renal disease completed the study. In a random fashion, one group was treated for 4 months with 4 mg of rosiglitazone first followed by a 4-month period of standard treatment. The opposite order was used for the second group., Results: Baseline urinary protein excretion rate was 1.45 g/24 h. On rosiglitazone, there was a drop of urinary protein level of 0.24 g/24 h (P=0.045). In contrast, there was a trend for proteinuria to increase during the control period (0.12 g/24 h, P=0.18). The urine protein level on rosiglitazone was lower than on usual treatment (0.36 g/24 h, P=0.002, 95% CI 0.15-0.58). There was a similar beneficial effect on systolic blood pressure which was reduced by rosiglitazone by 7.8 mmHg (P=0.006, 95% CI 2.6-13.1). Although average fasting glucose was only 5.8 mmol/L, there was a significant Spearman correlation between fasting glucose and a reduction in urinary protein levels (r=0.34, P=0.045)., Conclusion: It is concluded that thiazolidinediones may have a role in the management of non-diabetic proteinuria of various aetiologies. In this study the average body mass index was 28.9 kg/m2. It will be important to repeat these studies in non-overweight subjects with non-diabetic proteinuria and in addition to trial maximal therapeutic doses of the thiazolidenedione.

Background: Inflammation is implicated in cardiovascular disease (CVD) and mortality in end-stage renal failure (ESRF). Its importance in early renal disease is yet to be defined., Methods: Serum levels of systemic and vascular inflammatory markers in early IgA nephropathy (IgAN) and control subjects were measured and related to renal function and vascular risk factors. A parallel study in type 1 diabetes mellitus subjects with (T1DM Nx) and without nephropathy (T1DM No Nx) was performed., Results: Fifty-one IgAN patients aged 46+/-2 years (mean+/-SEM), calculated creatinine clearance (CrCl) 88+/-5 ml/min, were compared with 51 matched control subjects. Forty-six T1DM Nx patients aged 40+/-2 years, CrCl 84+/-5 ml/min, and 73 T1DM No Nx patients aged 38+/-2 years were also compared. High sensitivity C-reactive protein (hsCRP) was elevated in IgAN, T1DM Nx and T1DM No Nx patients compared with controls [4.2+/-0.6 (P < 0.001), 4.1+/-0.6 (P < 0.001), 2.6+/-0.4 (P < 0.05) vs 1.6+/-0.3 mg/l]. Levels in T1DM Nx patients were higher than in T1DM No Nx patients (P < 0.05). Inflammation and vascular dysfunction as measured by pulse pressure (PP) were related. HsCRP correlated with PP in IgAN and T1DM Nx (r = 0.47, P = 0.001; r = 0.40, P < 0.05). PP was the strongest independent predictor of hsCRP in IgAN (T = 2.45, P < 0.001), while body mass index (T = 7.83, P < 0.001) was the strongest predictor in T1DM Nx. Endothelial cell adhesion molecules were increased in T1DM Nx > IgAN > T1DM No Nx vs controls: soluble vascular adhesion molecule-1 (sVCAM-1) 760+/-30 (P < 0.001) > 663+/-34 (P = 0.001) > 601+/-21 (P < 0.05) vs 536+/-15 ng/ml; soluble intracellular adhesion molecule-1 (sICAM-1) 320+/-8 (P < 0.001) > 313+/-13 (P < 0.001) > 307+/-8 (P < 0.001) vs 244+/-6 ng/ml. sVCAM-1 levels were higher in T1DM Nx than in T1DM No Nx, P < 0.001. In IgAN and T1DM Nx, hsCRP correlated with sICAM-1 (r = 0.33, P = 0.017; r = 0.37; P = 0.017). sVCAM-1 was related to renal function in IgAN and T1DM Nx: serum cystatin C (r = 0.63, P < 0.001: r = 0.425, P = 0.002), and urine protein:creatinine ratio in IgAN (r = 0.48; P = 0.001)., Conclusions: Systemic and vascular markers of inflammation are increased in early renal disease and relate to renal dysfunction and cardiovascular risk factors. Inflammation may be a common process in various renal diseases and may link and accelerate renal dysfunction and CVD.

Background: Greek migrants to Australia have low all-cause and cardiovascular disease (CVD) mortality. This may be partly due to maintenance of a traditional Mediterranean diet and its interaction with CVD risk factors. The enzyme paraoxonase-1 (PON1) is thought to contribute to the anti-atherogenic properties of high density lipoproteins (HDL) by metabolizing lipid peroxides. PON1 activity is subject to modulation by dietary and genetic factors., Aims: To determine PON1 activity in Greek migrants and Anglo-Celtic subjects recruited from the Melbourne Collaborative Cohort Study, and its relationship to coronary risk factors and dietary markers., Methods: Greek (n = 127) and Anglo-Celtic (n = 128) participants in the MCCS were recruited. By design, there were approximately equal numbers of men and women and of diabetic and non-diabetic subjects. Subjects were screened for glucose tolerance, dyslipidaemia, hypertension and coronary heart disease. Plasma markers of diet (carotenoids, retinol, tocopherol, homocysteine) and inflammation (C-reactive protein) were assessed. Serum PON1 activity was determined spectrophotometrically using two substrates: paraoxon (paraoxonase) and phenylacetate (arylesterase)., Results: PON1 activity was significantly higher in the presence of hyperlipidaemia but otherwise did not vary by ethnicity, presence of coronary heart disease, diabetes, hypertension or smoking. Among subjects with the high activity phenotype (defined by the ratio of paraoxonase:arylesterase activity), paraoxonase activity correlated directly with circulating diet-derived carotenoid concentrations for Greeks, and inversely with homocysteine and C-reactive protein for Anglo-Celtics. No such associations were seen among subjects with the low activity phenotype., Conclusions: The data suggest that dietary modulation of atherosclerotic risk may vary according to PON1 phenotype.

Malignant cells are known to have accelerated metabolism, high glucose requirements, and increased glucose uptake. Transport of glucose across the plasma membrane of mammalian cells is the first rate-limiting step for glucose metabolism and is mediated by facilitative glucose transporter (GLUT) proteins. Increased glucose transport in malignant cells has been associated with increased and deregulated expression of glucose transporter proteins, with overexpression of GLUT1 and/or GLUT3 a characteristic feature. Oncogenic transformation of cultured mammalian cells causes a rapid increase of glucose transport and GLUT1 expression via interaction with GLUT1 promoter enhancer elements. In human studies, high levels of GLUT1 expression in tumors have been associated with poor survival. Studies indicate that glucose transport in breast cancer is not fully explained by GLUT1 or GLUT3 expression, suggesting involvement of another glucose transporter. Recently, a novel glucose transporter protein, GLUT12, has been found in breast and prostate cancers. In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface. Trafficking of GLUT12 to the plasma membrane could therefore contribute to glucose uptake. Several factors have been implicated in the regulation of glucose transporter expression in breast cancer. Hypoxia can increase GLUT1 levels and glucose uptake. Estradiol and epidermal growth factor, both of which can play a role in breast cancer cell growth, increase glucose consumption. Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells. Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer., (2004 Wiley-Liss, Inc.)

Background: An increasing number of arterial function assessments are available, including small and large arterial elasticity (SAE/C2, LAE/C1), endothelial function as measured by flow mediated dilation (FMD), carotid intima-medial thickness (IMT), ankle brachial index (ABI), pulse pressure (PP), and pulse wave velocity (PWV). We have consecutively performed these measures in subjects with low and high vascular disease risks to assess the interrelationships., Methods and Results: Twenty healthy subjects (HS) and 20 older subjects with type 2 diabetes mellitus (DM) were studied with all techniques at a single sitting by a single operator. In HS, C2 correlated with FMD (R = 0.577, P = .008), PWV (R = 0.522, P = .046), and ABI (R = 0.463, P = .04). There was no significant correlation of C1 and FMD or blood pressure (BP) measurements. In DM, C2 correlated with FMD (R = 0.443, P = .05), systolic BP (R = -0.553, P = .01), PP (R = -0.601, P = .005), and systemic vascular resistance (R = -0.577, P = .008). There was no significant correlation between anthropometric measures and arterial function measures in either group. The IMT was not correlated with any measure of arterial function in either group., Conclusions: C2 assessed by pulse wave analysis correlated with endothelial function measured by FMD in young apparently healthy subjects and older subjects with type 2 diabetes. Systolic BP and PP correlated with C2 and FMD in older diabetic subjects but not healthy subjects. The interrelationships between arterial function measures are different in high and low risk populations. This variability needs to be considered when applying these techniques to individuals in different populations.

Background: Disease management programs in which drugs are prescribed by dietitians or nurses have been shown to improve the coronary risk factor profile in patients with coronary heart disease. However, those disease management programs in which drugs are not prescribed by allied health professionals have not improved coronary risk factor status. The objective of the Coaching patients On Achieving Cardiovascular Health (COACH) study was to determine whether dietitians or nurses who did not prescribe medications could coach patients with coronary heart disease to work with their physicians to achieve the target levels for their total cholesterol (TC) and other risk factors., Methods: Multicenter randomized controlled trial in which 792 patients from 6 university teaching hospitals underwent a stratified randomization by cardiac diagnosis within each hospital: 398 were assigned to usual care plus The COACH Program and 394 to usual care alone. Patients in The COACH Program group received regular personal coaching via telephone and mailings to achieve the target levels for their particular coronary risk factors. There was one coach per hospital. The primary outcome was the change in TC (DeltaTC) from baseline (in hospital) to 6 months after randomization. Secondary outcomes included measurement of a wide range of physical, nutritional, and psychological factors. The analysis was performed by intention to treat., Results: The COACH Program achieved a significantly greater DeltaTC than usual care alone: the mean DeltaTC was 21 mg/dL (0.54 mmol/L) (95% confidence interval [CI], 16-25 mg/dL [0.42-0.65 mmol/L]) in The COACH Program vs 7 mg/dL (0.18 mmol/L) (95% CI, 3-11 mg/dL [0.07-0.29 mmol/L]) in the usual care group (P<.0001). Thus, the reduction in TC from baseline to 6 months after randomization was 14 mg/dL (0.36 mmol/L) (95% CI, 8-20 mg/dL [0.20-0.52 mmol/L]) greater in The COACH Program group than in the usual care group. Coaching produced substantial improvements in most of the other coronary risk factors and in patient quality of life., Conclusions: Coaching, delivered as The COACH Program, is a highly effective strategy in reducing TC and many other coronary risk factors in patients with coronary heart disease. Coaching has potential effectiveness in the whole area of chronic disease management.

Objective: To describe the levels of inflammation and vascular endothelial activation in an Aboriginal community, and the relationship of these factors to coronary heart disease (CHD) risk factors and markers of nutritional quality., Design and Participants: A cross-sectional survey of 95 women and 76 men participating in a chronic-disease prevention program., Setting: A remote Aboriginal community in Western Australia in 1996., Main Outcome Measures: Concentrations of markers of inflammation (C-reactive protein [CRP]) and vascular endothelial activation (soluble E-selectin [sE-selectin]); presence of metabolic syndrome; concentrations of diet-derived antioxidants., Results: Participants exhibited very high plasma concentrations of CRP (mean, 5.4 mg/L; 95% CI, 4.6-6.3 mg/L) and sE-selectin (mean, 119 ng/mL; 95% CI, 111-128 ng/mL). Both CRP and sE-selectin concentrations were significantly higher in the presence of the metabolic syndrome. There were significant inverse linear relationships between concentrations of CRP and plasma concentrations of the antioxidants lycopene, beta-carotene, cryptoxanthin and retinol. Even stronger inverse associations were evident between concentrations of sE-selectin and lycopene, beta-carotene, cryptoxanthin and lutein., Conclusions: Vascular inflammation and endothelial activation may be important mediators of elevated CHD risk in Aboriginal people. Inadequate nutrition and physical inactivity may contribute to this process.

Background: Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen-dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells., Methods: Reverse transcription-polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4-2, and C4-2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12., Results: GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1., Conclusions: GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi association is that it may supply glucose to the Golgi for byproduct incorporation into the prostatic secretory fluid. Further work will investigate the importance of glucose transport and GLUT1 and GLUT12 in prostate carcinoma cell growth., (Copyright 2003 American Cancer Society.)

Microalbuminuria clusters with the metabolic syndrome, and both conditions predict cardiovascular disease mortality. The reported relationships of microalbuminuria with the individual components of the metabolic syndrome (i.e., hyperglycemia, insulin resistance, hypertension, dyslipidemia, abdominal obesity) are variable. Each of these components, as well as intrauterine effects and diet and other lifestyle factors, may contribute to elevated risk of microalbuminuria in certain population groups. Recent evidence indicates a role for oxidation and inflammation in cardiovascular disease, and endothelial dysfunction (exacerbated by factors such as dyslipidemia) may be the mediator of this relationship. Because endothelial dysfunction can also be manifested as microalbuminuria, this provides a potential explanation of the observed association of the metabolic syndrome, chronic inflammation, and microalbuminuria.

Glucose plays a major role in mammary gland function during lactation as it is used both as a fuel and as a precursor of milk components. In rats, previous studies have shown that the facilitative glucose transporter GLUT1 is expressed in mammary epithelial cells. We have used confocal immunofluorescence to localise GLUT1 and GLUT12, a recently identified member of the sugar transporter family, in pregnant and lactating rat mammary gland. GLUT12 staining was observed in the cytoplasm of mammary epithelial cells at day 20 of pregnancy, and at 1 and 6 days postpartum. Furthermore, GLUT12 staining was present at the apical plasma membrane of epithelial cells during lactation. In contrast, GLUT1 protein localised to the cytoplasm and basolateral surface of mammary epithelial cells. Forced weaning resulted in decreased cytoplasmic GLUT1 staining intensity, but no change in GLUT12 staining. The results suggest a possible role for GLUT12 in the metabolism of mammary epithelial cells during pregnancy and lactation.

Glucose is an essential molecule for most mammalian cells, and is particularly important during fetal development, when cells are rapidly dividing and differentiating. In rats, GLUT1 is present at high levels in most fetal tissues, with levels decreasing after birth. We used immunohistochemistry to localise GLUT12 protein, a recently identified member of the sugar transporter family, and GLUT1 during rat fetal development. GLUT12 staining was observed in heart muscle from gestational days 15 to 21. GLUT12 staining in skeletal muscle increased from gestational days 17 to 21, and GLUT12 was also detected in brown adipose tissue. The expression of GLUT12 in insulin-responsive tissues supports a potential role for GLUT12 in the provision of glucose to these tissues before the appearance of GLUT4. GLUT12 protein was also expressed in fetal chondrocytes from gestational day 15 onward, in kidney distal tubules and collecting ducts from day 19, and in lung bronchioles from day 19. The specific pattern of expression observed in the rat fetus suggests that GLUT12 may be important in hexose delivery to developing tissues.

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.

Objective: To describe the lifestyle-related chronic disease and risk factor prevalence among Torres Strait Islander people of the Torres Strait and Northern Peninsula Area Health Service District and to compare this information with that available for the general Australian population., Methods: Voluntary community-based screening for persons aged 15 years and older, including oral glucose tolerance test, anthropometry, health questionnaire, measurement of lipids and lipoprotein levels, blood pressure and urinary albumin to creatinine ratio., Results: Nine communities participated in screening between 1993 and 1997. Five hundred and ninety-two participants (286 male and 306 female) identified as Torres Strait Islander. There were high prevalences of overweight (30%), obesity (51%), abdominal obesity (70%), diabetes (26%), hypercholesterolaemia (33%), albuminuria (28%), hypertension (32%) and tobacco smoking (45%). Only 8.5% of men and 6.5% of women were free of any cardiovascular risk factors (abdominal obesity, hypercholesterolaemia, hypertension, dyslipidaemia, smoking, diabetes, albuminuria). Comparisons of this information for Torres Strait Islander people with results from the AusDiab survey show rates of obesity three times higher and diabetes six times higher than for other Australians., Conclusions: There is a very high prevalence of preventable chronic disease and associated risk factors among Torres Strait Islander people of the Torres Strait and Northern Peninsula Area., Implications: Effective interventions to prevent and manage obesity, diabetes and associated cardiovascular risk factors are essential if the health of the Torres Strait Islander people is to improve. Such interventions could inform initiatives to stem the burgeoning epidemic of obesity and diabetes among all Australians.

Objectives: To determine the proportion of patients with established coronary heart disease (CHD) in two Australian studies (VIC-I in 1996-1998, and VIC-II in 1999-2000) who achieved their risk-factor targets as recommended by the National Heart Foundation of Australia, and to compare this proportion with those in studies from the United Kingdom (ASPIRE), Europe (EUROASPIRE I and II) and the United States (L-TAP)., Design and Setting: Prospective cohort study with VIC-I set in a single Melbourne university teaching hospital and VIC-II set in six university teaching hospitals in Melbourne, Victoria., Participants: 460 patients (112 in VIC-I, 348 in VIC-II) who completed follow-up in the control groups of two randomised controlled trials of a coaching intervention in patients with established CHD., Main Outcome Measures: The treatment gap (100%, minus the percentage of patients achieving the target level for a particular modifiable risk factor) at six months after hospitalisation., Results: The treatment gap declined from 96.4% (95% CI, 91%-99%) to 74.1% (95% CI, 69%-79%) for total cholesterol concentration (TC) < 4.0 mmol/L (P = 0.0001) and from 90.2% (95% CI, 83%-95%) to 54.0% (95% CI, 49%-59%) for TC < 4.5 mmol/L (P = 0.0001). This reduction in the treatment gap between VIC-I and VIC-II appears to be entirely explained by an increase in the number of patients prescribed lipid-lowering drugs. The treatment gaps in the UK and two European studies were substantially greater. The treatment gap for blood pressure (systolic > or = 140 mmHg and/or diastolic > or = 90 mmHg) in VIC-II was 39.5%, again less than corresponding European data. There were 8.1% of patients who had unrecognised diabetes in VIC-II (fasting glucose level > or = 7 mmol/L), making a total of 25.6% of VIC-II patients with diabetes, self-reported or unrecognised. The proportion of patients in VIC-II who were obese (body mass index > or = 30 kg/m2) was similar to the overseas studies, while fewer patients in VIC-II smoked compared with those in the UK and European studies., Conclusions: A substantial treatment gap exists in Victorian patients with established CHD. The treatment gap compares well with international surveys and, at least in the lipid area, is diminishing.

Community studies have demonstrated suboptimal achievement of lipid targets in the management of patients with coronary heart disease (CHD). An effective strategy is required for the application of evidence-based prevention therapy for CHD. The objective of this study was to test coaching as a technique to assist patients in achieving the target cholesterol level of <4.5 mmol/L. Patients with established CHD (n = 245) underwent a stratified randomization by cardiac procedure (coronary artery bypass graft surgery or percutaneous coronary intervention) to receive either the coaching intervention (n = 121) or usual medical care (n = 124). The primary outcome measure was fasting serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and calculated low-density lipoprotein cholesterol (LDL-C) level, measured at 6 months post-randomization. At 6 months, the serum TC and LDL-C levels were significantly lower in the coaching intervention group (n = 107) than the usual care group (n = 112): mean TC (95%CI) 5.00 (4.82-5.17) mmol/L versus 5.54 (5.36-5.72) mmol/L (P <.0001); mean LDL-C (95%CI) 3.11 (2.94-3.29) mmol/L versus 3.57 (3.39-3.75) mmol/L (P <.0004), respectively. Coaching had no impact on TG or on HDL-C levels. Multivariate analysis showed that being coached (P <.001) had an effect of equal magnitude to being prescribed lipid-lowering drug therapy (P <.001). The effectiveness of the coaching intervention is best explained by both adherence to drug therapy and to dietary advice given. Coaching may be an appropriate method to reduce the treatment gap in applying evidence-based medicine to the "real world."