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Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E−/− mice. Kidney biopsies were used to examine infiltration of KIM-1–expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0–10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes sho

Background By 2025, it is estimated that approximately 1.8 million Australian adults (approximately 8.4% of the adult population) will have diabetes, with the majority having type 2 diabetes. Weight management via improved physical activity and diet is the cornerstone of type 2 diabetes management. However, the majority of weight loss trials in diabetes have evaluated short-term, intensive clinic-based interventions that, while producing short-term outcomes, have failed to address issues of maintenance and broad population reach. Telephone-delivered interventions have the potential to address these gaps. Methods/Design Using a two-arm randomised controlled design, this study will evaluate an 18-month, telephone-delivered, behavioural weight loss intervention focussing on physical activity, diet and behavioural therapy, versus usual care, with follow-up at 24 months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes, will be recruited from 10 general practices via electronic medical records search. The Social-Cognitive Theory driven intervention involves a six-month intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and 24 months, are: weight loss, physical activity, and glycaemic control (HbA1c), with weight loss and physical activity also measured at 12 months. Incremental cost-effectiveness will also be examined. Study recruitment began in February 2009, with final data collection expected by February 2013. Discussion This is the first study to evaluate the telephone as the primary method of delivering a behavioural weight loss intervention in type 2 diabetes. The evaluation of maintenance outcomes (6 months following the end of intervention), the use of accelerometers to objectively measure physical activity, and the inclusion of a cost-effectiveness analysis will advance the science of broad reach approaches to weight control and health behavi

Background By 2025, it is estimated that approximately 1.8 million Australian adults (approximately 8.4% of the adult population) will have diabetes, with the majority having type 2 diabetes. Weight management via improved physical activity and diet is the cornerstone of type 2 diabetes management. However, the majority of weight loss trials in diabetes have evaluated short-term, intensive clinic-based interventions that, while producing short-term outcomes, have failed to address issues of maintenance and broad population reach. Telephone-delivered interventions have the potential to address these gaps. Methods/Design Using a two-arm randomised controlled design, this study will evaluate an 18-month, telephone-delivered, behavioural weight loss intervention focussing on physical activity, diet and behavioural therapy, versus usual care, with follow-up at 24 months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes, will be recruited from 10 general practices via electronic medical records search. The Social-Cognitive Theory driven intervention involves a six-month intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and 24 months, are: weight loss, physical activity, and glycaemic control (HbA1c), with weight loss and physical activity also measured at 12 months. Incremental cost-effectiveness will also be examined. Study recruitment began in February 2009, with final data collection expected by February 2013. Discussion This is the first study to evaluate the telephone as the primary method of delivering a behavioural weight loss intervention in type 2 diabetes. The evaluation of maintenance outcomes (6 months following the end of intervention), the use of accelerometers to objectively measure physical activity, and the inclusion of a cost-effectiveness analysis will advance the science of broad reach approaches to weight control and health behavi

Objective: To measure adherence to a specific exercise prescription (1500 kcal week- 1) by objectively quantifying unsupervised exercise energy expenditure (ExEE) in obese women. Design: The 16-week lifestyle intervention consisted of weekly meetings with research staff and promotion of increased ExEE (1500 kcal week- 1) and a decreased dietary intake (- 500 kcal day- 1). Participants: Twenty-nine obese females (body mass index=36.85.0 kg m- 2, body fat=49.63.7% ) from a hospital-based lifestyle intervention were included in the analysis. Measurements: ExEE was estimated and monitored weekly using heart rate monitoring, and body composition was measured before and after the intervention by dual-energy X-ray absorptiometry. Results: Free-living adherence to the exercise prescription was variable and, on average, modest such that 14% achieved 1500 kcal week- 1, and the average weekly ExEE (768 kcal week- 1) represented 51.2% of the total amount prescribed. ExEE was correlated with changes in body weight (r=0.65, P<0.001) and fat mass (r=0.65, P<0.001). Achievement of a 5% weight loss target was dependent on the achievement of an ExEE level of 1000 kcal week- 1 (P<0.001). Exercise 'adherers' (>1000 kcal week- 1) lost more weight (- 9.9 vs - 4.1 kg), more fat mass (- 6.8 vs - 3.0 kg) and more waist circumference (- 9.8 vs - 5.6 cm) when compared to 'non-adherers' (<1000 kcal week- 1). Discussion: Exercise is an integral component of lifestyle interventions aimed at reducing obesity and its complications. However, without accurate and objective measures of ExEE, it is difficult for relationships between exercise and health outcomes to be elucidated. The present study suggests an alternative to self-report to increase the confidence with which conclusions are drawn regarding the role of exercise within lifestyle interventions.

Subclinical myocardial and vascular dysfunctions occur in subjects with obesity. We investigated whether these changes were reversible with weight loss due to lifestyle intervention. Quantitative assessment of myocardial and vascular functions was performed at baseline and after a minimum of 8 weeks of a lifestyle intervention program in 106 subjects with significant risk factors but no history of cardiovascular disease and normal ejection fractions. Myocardial function was assessed using strain rate, strain, regional myocardial systolic velocity, and diastolic velocity (em). Myocardial reflectivity was assessed by calibrated integrated backscatter. Vascular function was assessed using brachial arterial reactivity and arterial compliance. Exercise capacity was measured by peak oxygen consumption per unit time (VO2). Weight loss (−4.5 ± 2.0%) was achieved by 48 subjects, and 58 maintained or increased weight (+1 ± 1.5%, p <0.001). Compared with the stable weight group, the weight loss group showed significant improvement in brachial arterial reactivity (8.6 ± 4.9% vs 6.7 ± 4.9%, p <0.05), em (6.4 ± 1.9 vs 5.5 ± 1.9 cm/s, p <0.01), and reflectivity (calibrated integrated backscatter, 18.3 ± 4.9 vs 16.2 ± 5.2 dB, p <0.01). The magnitude of weight change correlated with changes in em (r = 0.36) and calibrated integrated backscatter (r = 0.33). The change in em correlated with peak VO2 (r = 0.38, p <0.001) and was an independent predictor for peak VO2 even after adjustment for age and body mass index in a multivariate model (R2 = 0.45, p <0.001). Weight loss was not associated with a significant change in systolic parameters (regional myocardial systolic velocity, global strain, and strain rate) or arterial compliance.

Objective: To investigate the effect of an 8 week group based cognitive behaviour therapy intervention on change in weight and other weight related variables, change in physical activity and change in health and well being compared to individualised dietetic treatment or giving information only Design: A randomised control trial with an 8-week intervention period – two intervention groups, a group based cognitive behaviour therapy intervention, Fat Booters Inc – (FBI) and individualised dietetic treatment (IDT) and control group receiving an information booklet only (BO). Intervention for 8 weeks with monthly follow-up to 6 months and further follow-up at 12 months, conducted in real practice setting. Subjects: A total of 176 adults with body mass index (BMI) > 27kg/m2, mean (+/-SD) age 48+/-13 years, mean BMI 34+/-5.5 kg/m2. Main Outcome Measures: Weight, percent body fat, waist circumference, physical activity, health status, self-efficacy and satisfaction with life were measured at baseline, 3, 6 and 12 months. Results: A statistically significant difference between groups was observed for weight change over time (p = 0.05). The change in weight (mean ± se) for the FBI group was significantly greater than the BO group at 6 and 12 months (-2.8 ± 0.7 compared to –1.0 ± 0.6 kg, p<0.05 and –2.9 ± 0.9 compared to +0.5 ± 0.9 kg, p<0.005, respectively). Change in weight in the IDT group did not differ from the FBI group at any time point. For all groups, waist circumference was significantly less than baseline at all time points (p<0.001). Significant differences in self-efficacy were observed over time (p=0.02), with both intervention groups having greater self-efficacy than the BO group. Significant drop-outs occurred over time for all three groups. Conclusions: A cognitive behaviour based intervention was more effective than providing information alone and as effective as intensive individualised dietetic intervention in weight loss and improvements in self-efficacy.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism. We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD. Methods: Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane, Australia from 2011 through 2012. They were randomly assigned to groups given 3000 mg resveratrol (n= 10) or placebo (n= 10) daily for 8 weeks. Outcomes included insulin resistance (assessed by the euglycemic-hyperinsulinemic clamp), hepatic steatosis, and abdominal fat distribution (assessed by magnetic resonance spectroscopy and imaging). Plasma markers of inflammation, as well as metabolic, hepatic, and antioxidant function, were measured; transcription of target genes was measured in peripheral blood mononuclear cells. Resveratrol pharmacokinetics and safety were assessed. Results: Eight-week administration of resveratrol did not reduce insulin resistance, steatosis, or abdominal fat distribution when compared with baseline. No change was observed in plasma lipids or antioxidant activity. Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group. Resveratrol did not significantly alter transcription of NQO1, PTP1B, IL6, or HO1 in peripheral blood mononuclear cells. Resveratrol was well-tolerated. Conclusions: Eight weeks administration of resveratrol did not significantly improve any features of NAFLD, compared with placebo, but it increased hepatic stress, based on obser