OBJECTIVE:Bariatric surgery is an effective treatment for type 2 diabetes and morbid obesity. This paper analyses the clinical and patient-reported outcomes of patients treated through the Bariatric Surgery Initiative, a health system collaboration providing bariatric surgery as a state-wide public service in Queensland, Australia.RESEARCH DESIGN AND METHODS:A longitudinal prospective cohort study was undertaken. Eligible patients had type 2 diabetes and morbid obesity (BMI ≥ 35 kg/m2). Following referral by specialist outpatient clinics, 212 patients underwent Roux-en-Y gastric bypass or sleeve gastrectomy. Outcomes were tracked for a follow-up of 12-months and included body weight, BMI, HbA1c, comorbidities, health-related quality of life, eating behaviour, and patient satisfaction.RESULTS:Following surgery, patients' average body weight decreased by 23.6%. Average HbA1c improved by 24.4% and 48.8% of patients were able to discontinue diabetes-related treatment. The incidence of hypertension, non-alcoholic steatohepatitis, and renal impairment decreased by 37.1%, 66.4%, and 62.3%, respectively. Patients' emotional eating scores, uncontrolled eating and cognitive restraint improved by 32.5%, 20.7%, and 6.9%, respectively. Quality of life increased by 18.8% and patients' overall satisfaction with the treatment remained above 97.5% throughout the recovery period.CONCLUSIONS:This study confirmed previous work demonstrating the efficacy of publicly funded bariatric surgery in treating obesity, type 2 diabetes and related comorbidities, and improving patients' quality of life and eating behaviour. Despite the short follow-up period, the results bode well for future weight maintenance in this cohort.

Myocardial dysfunction can progress to heart failure and structural heart disease without the presence of coronary artery disease. In this study we investigated the correlates and predictors of changes in myocardial function between obese, renal transplant and type 2 diabetes patients.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of kidney disease (DKD). In Type 1 diabetes, increased uACR (urinary albumin-creatinine ratio) 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 yrs; M:F-54:46, HbA1C-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m-2] and 10 year historical uACR, HbA1C and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to 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 (uACRAUC0-10yrs, 29.7±8.8 vs 4.5±0.5; P<0.01 vs low risk) and early kidney dysfunction including ~8.3ml.min-1.1.73m-2 higher estimated glomerular filtration rates (eGFRSCHWARTZ; 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 showed elevated collagen IV and SGLT2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T cell production of KIM-1.

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes ( N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m 2 ) and healthy controls ( N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m 2 ) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFR CKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI ( P model = 1.5 × 10 –12 ). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk ( P model = 2.2 × 10 –9 ), which increased with diabetes duration (51%; P model < 2.2 × 10 –16 ) and random blood glucose concentrations (56%; P model < 2.2 × 10 –16 ). HbA 1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.

BACKGROUND:Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM).AIMS:To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes.METHODS:Over a 12-month period, young adults (18-25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID-20) questionnaire, the Patient Health Questionnaire-4 (PHQ-4) and the World Health Organization Well-Being Index-5 (WHO-5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included.RESULTS:Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes-related distress (PAID-20 ≥ 40) was found in 19.4%. Low WHO-5 scores (28-50 points) were seen in 14.8%. PHQ-4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%.CONCLUSION:DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team.

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Background Routine psychosocial screening and management of people with diabetes is recommended. Aims To profile demographic, medical and psychosocial characteristics of young people with diabetes, and to develop a screening tool and care pathway for routine use. Methods Indices of diabetes control and recorded diabetes complications were complimented by psychosocial screening tools assessing psychological, diabetes specific and perceived stress (Kessler 10, Problem Area in Diabetes, Perceived Stress Scale), well‐being (World Health Organization Well Being Index‐5), disordered eating (Eating Disorder Risk Inventory‐3 Risk Composite), compensatory behaviour questionnaire, social support (Multidimensional Scale of Perceived Social Support), resilience (Connor Davidson Resilience Scale – 2 item) and financial concerns. Service provision and demographic data were also collected. Diabetes and mental health clinicians then identified a subset of measures to use for routine screening along with care pathways. Results Psychosocial screening was well accepted. Participants (151) had suboptimal glycaemic control (glycated haemoglobin 8.0 interquartile range 1.8%/64 interquartile range 22 mmol/mol). Severe diabetes‐related distress (Problem Area in Diabetes ≥40) was found in 19.4% and 26.0% reported difficulties managing healthcare costs. A mental health disorder was likely in 9.7%, whilst 23.4% had high Kessler 10 scores. Low World Health Organization Well Being Index‐5 scores (≤13) were seen in 29.0%. Risk for an eating disorder (Eating Disorder Risk Inventory‐3 Risk Composite) was 12.7%, whereas approximately 36.0% had disturbed eating behaviours. Conclusion Psychosocial screening of young adults with diabetes identified complex needs. A brief psychosocial screening tool and associated care pathways were developed for routine use in a young adult tertiary referral diabetes clinic. The tool assesses constructs, such as diabetes distress, depression, anxiety, well‐being, hypoglycaemia‐unawareness, fear of hypoglycaemia, social support, weight, shape and eating concerns and financial concerns. This will provide a longitudinal data source for further research to inform clinical practice.

AIMTo investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease (NAFLD). METHODSParticipants were randomised into either circuit exercise training (EX; n = 13; 3 h/wk without changes in dietary habits), or dietary energy restriction (ER) without changes in structured physical activity (ER; n = 8).Respiratory quotient (RQ) and whole-body fat oxidation rates (Fatox) were determined by indirect calorimetry under basal, insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology; hepatic Fatox was estimated from plasma β-hydroxybutyrate concentrations; cardiorespiratory fitness was expressed as VO2peak.Complete-case analysis was performed (EX: n = 10; ER: n = 6). RESULTSHepatic steatosis and NAFLD activity score decreased with ER but not with EX. β-hydroxybutyrate concentrations increased significantly in response to ER (0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L, P = 0.03) but remained unchanged in response to EX (0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L, P = 0.39).Basal RQ decreased (P = 0.05) in response to EX, while this change was not significant after ER (P = 0.38).VO2peak (P < 0.001) and maximal Fatox during aerobic exercise (P = 0.03) improved with EX but not with ER (P > 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis (r = -0.56,P = 0.04). CONCLUSIONER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fatox in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.

The SCALE Obesity and Prediabetes (NCT01272219) trial randomized adults with prediabetes and obesity (BMI ≥30 kg/m2) or overweight with comorbidities (≥27 kg/m2; dyslipidemia/hypertension) to liraglutide 3.0 mg (N=1505) or placebo (N=749) as adjunct to diet and exercise for 3 years. This post hoc analysis compared liraglutide 3.0 mg early responders (ERs; ≥5% weight loss [WL] at Week [W] 16) and early non-responders (ENRs; <5% WL at W16), in keeping with EMA and Canadian stopping-rule criteria. Efficacy outcomes are estimated means in ERs (n=580) and ENRs (n=210) who completed 160 weeks' treatment. Those developing T2D/regression to normoglycemia were analyzed on the full analysis set with LOCF. Safety was based on the safety analysis set. Placebo data are shown only for proportion of ERs/ENRs.

This 3-year trial investigated the effect of liraglutide 3.0 mg, as an adjunct to diet and exercise (D&E), in delaying the onset of T2D (primary endpoint) in adults with prediabetes and obesity (BMI ≥30 kg/m2) or overweight (≥27 kg/m2) with comorbidities.

Intramyocellular lipids (IMCL) are depleted in response to an acute bout of exercise in lean endurance-trained individuals; however, it is unclear whether changes in IMCL content are also seen in response to acute and chronic exercise in obese individuals. We used magnetic resonance spectroscopy in 18 obese men and 5 normal-weight controls to assess IMCL content before and after an hour of cycling at the intensity corresponding with each participant's maximal whole-body rate of fat oxidation (Fatmax). Fatmax was determined via indirect calorimetry during a graded exercise test on a cycle ergometer. The same outcome measures were reassessed in the obese group after a 16-week lifestyle intervention comprising dietary calorie restriction and exercise training. At baseline, IMCL content decreased in response to 1 h of cycling at Fatmax in controls (2.8 ± 0.4 to 2.0 ± 0.3 A.U., -39%, p = 0.02), but not in obese (5.4 ± 2.1 vs. 5.2 ± 2.2 A.U., p = 0.42). The lifestyle intervention lead to weight loss (-10.0 ± 5.4 kg, p < 0.001), improvements in maximal aerobic power (+5.2 ± 3.4 mL/(kg·min)), maximal fat oxidation rate (+0.19 ± 0.22 g/min), and a 29% decrease in homeostasis model assessment score (all p < 0.05). However, when the 1 h of cycling at Fatmax was repeated after the lifestyle intervention, there remained no observable change in IMCL (4.6 ± 1.8 vs. 4.6 ± 1.9 A.U., p = 0.92). In summary, there was no IMCL depletion in response to 1 h of cycling at moderate intensity either before or after the lifestyle intervention in obese men. An effective lifestyle intervention including moderate-intensity exercise training did not impact rate of utilisation of IMCL during acute exercise in obese men.

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 observed increases in levels of liver enzymes. Further studies are needed to determine whether agents that are purported to mimic calorie restriction, such as resveratrol, are safe and effective for complications of obesity.

Aims: Type 2 diabetes is a risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). Lifestyle intervention is the principal treatment for NAFLD however the effects of exercise alone on the histological and metabolic severity of NAFLD are unclear. This study assessed the effects of 6 months exercise training and diet-induced weight loss on insulin resistance and liver histologyin overweight patients with NAFLD.Methods: 21 patients were randomised to circuit exercise (EX) training (60 minx3/week) or dietary induced weight loss (DIWL) (-500 kcal/d). Insulin sensitivity (euglycaemic-hyperinsulinemic clamp with tracer), adiposity (CT scan) and histology (liver biopsy) were assessed at 0 and 6 months.Results: Weight decreased by 9.7 +/- 4.6% (-6.7 +/- 6.3 kg p=0.02) with DIWL but was unchanged after EX. Both groups equivalently reduced visceral fat (DIWL -22 +/- 24% p=0.06 and EX -18 +/- 18% p<0.05) while only EX increased lean mass (+ 3% p<0.01). DIWL markedly reduced steatosis (73 +/- 36% to 23 +/- 32%, p<0.05) and NAFLD activity score NAS (median (range) 5 (1-7) to 1 (0-5), p<0.05). After EX, there was no change in steatosis or NAS. A decrease in steatosis was associated with weight loss (r(s) =0.82, p<0.0001). An improvement in fibrosis was associated with a decrease in steatosis (r(s) =0.64, p=0.02). Small improvements in fasting hepatic insulin resistance were similar in both groups while changes in muscle insulin resistance were not significant.Conclusions: Circuit exercise is safe and efficacious for improving cardiometabolic risk factors in patients with NAFLD, however this dose of circuit training, without concomitant weight loss, was insufficient for histological improvements in NAFLD. The pilot study outcomes should stimulate further development of different exercise protocols (type, frequency and intensity) to address disease-specific conditions in those with severe insulin resistance.

There has been substantial recent interest in using vitamin D to improve insulin sensitivity and preventing/delaying diabetes in those at risk. There is little consensus on the physiological mechanisms and whether the association is direct or indirect through enhanced production of insulin-sensitising chemicals, including adiponectin. We examined cross-sectional associations between serum 25-hydroxyvitamin D (25(OH)D) and insulin sensitivity (Matsuda index), parathyroid hormone (PTH), waist circumference, body mass index (BMI), triglycerides (TG), total and high molecular weight (HMW) adiponectin, HMW : total adiponectin ratio (HMW : total adiponectin), and total cholesterol : HDL cholesterol ratio (TC:HDL cholesterol) in 137 Caucasian adults of mean age 43.3 ± 8.3 years and BMI 38.8 ± 6.9 kg/m(2). Total adiponectin (standardised β = 0.446; p < 0.001), waist circumference (standardised β = -0.216; p < 0.05), BMI (standardised β = -0.212; p < 0.05), and age (standardised β = -0.298; p < 0.001) were independently associated with insulin sensitivity. Serum 25(OH)D (standardised β = 0.114; p = 0.164) was not associated with insulin sensitivity, total or HMW adiponectin, HMW : total adiponectin, or lipids. Our results provide the novel finding that 25(OH)D is not associated with HMW adiponectin or HMW : total adiponectin in nondiabetic, obese adults and support the lack of association between 25(OH)D and lipids noted by others in similar groups of patients.