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Lucy Gracen,1 Melanie Aikebuse,2,3 Babak Sarraf,2– 4 Steven M McPhail,5 Anthony W Russell,6 James O’Beirne,7 Katharine M Irvine,8 Suzanne Williams,9 Patricia C Valery,4,* Elizabeth E Powell2– 4,* 1Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; 3Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Australian Centre for Health Services Innovation School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia; 6Endocrinology and Diabetes, the Alfred Hospital, Melbourne, VIC, Australia; 7Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, Australia; 8Mater Research, Translational Research Institute, Brisbane, QLD, Australia; 9Inala Primary Care General Practice, Inala, QLD, Australia*These authors contributed equally to this workCorrespondence: Elizabeth E Powell, Centre for Liver Disease Research, Faculty of Medicine, Translational, Research Institute, The University of Queensland, Level 5, West Wing, 37, Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia, Tel +61 412 014 337, Email e.powell@uq.edu.auBackground: Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear.Methods: Sequential adults with T2D attending selected community clinics during 2021– 2023 were invited to receive a “liver health check” (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. “Template” letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants’ GPs.Results: Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥ 8), 15 participants with ‘red flags’ (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the “template” letters favourably on a Likert rating scale.Conclusion: The low rate of participation in the “liver health check” and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.Keywords: NAFLD, primary care, chronic liver disease, FibroScan

Jacqueline D Cotugno,1 Maree Ferguson,1,2 Hazel Harden,3 Shoni Colquist,3 Annabelle A Stack,1 Jane I Zimmerman,4 Anthony W Russell,4,5 Lauren E Ball,6 Ingrid J Hickman1,71Department of Nutrition and Dietetics, Princess Alexandra Hospital, 2School of Human Movement and Nutrition Sciences, The University of Queensland, 3INNIS Partnership, Brisbane, 4Department of Diabetes & Endocrinology, Princess Alexandra Hospital, 5School of Medicine, University of Queensland, 6Menzies Health Institute Queensland, Griffith University, 7The Mater Research Institute, The University of Queensland, Brisbane, QLD, AustraliaBackground: Insightful accounts of patient experience within a health care system can be valuable for facilitating improvements in service delivery.Objective: The aim of this study was to explore patients’ perceptions and experiences regarding a tertiary hospital Diabetes and Endocrinology outpatient service for the management of type 2 diabetes mellitus (T2DM).Method: Nine patients participated in discovery interviews with an independent trained facilitator. Patients’ stories were synthesized thematically using a constant comparative approach.Results: Three major themes were identified from the patients’ stories: 1) understanding T2DM and diabetes management with subthemes highlighting that specialist care is highly valued by patients who experience a significant burden of diabetes on daily life and who may have low health literacy and low self confidence; 2) relationships with practitioners were viewed critical and perceived lack of empathy impacted the effectiveness of care; and 3) impact of health care systems on service delivery with lack of continuity of care relating to the tertiary hospital model and limitations with appointment bookings negatively impacting on patient experience.Discussion: The patients’ stories suggest that the expectation of establishing a productive, ongoing relationship with practitioners is highly valued. Tertiary clinics for T2DM are well placed to incorporate novel technological approaches for monitoring and follow-up, which may overcome many of the perceived barriers of traditional service delivery.Conclusion: Investing in strategies that promote patient–practitioner relationships may enhance effectiveness of treatment for T2DM by meeting patient expectations of personalized care. Future changes in service delivery would benefit from incorporating patients as key stakeholders in service evaluation.Keywords: diabetes mellitus, discovery interview, health care, personal narratives

BACKGROUND: Both Roche and Abbott have released new glucose meter strips. They supply the entire Australian hospital market. The present study compared the performance of the new strips utilizing various specimen types (capillary, venous lithium heparin whole blood, venous lithium heparin plasma and serum) and evaluated how well they comply with the International Standards Organization (ISO) 15197 criteria. METHODS: The study included imprecision, patient comparison and interference studies. Participants with and without diabetes were recruited to evaluate the performance of various specimen types against the Beckman DxC800 glucose method. The strips were tested for different interferences: galactose, maltose, lactose, Icodextrin, Intragam, paracetamol, sodium, ascorbic acid, variable strip storage temperature, haematocrit, haemolysis and lipaemia. RESULTS: The imprecision of the two strips was approximately 5% or less, except for the Abbott strip at very low values (1.4 mmol/L), approximately 7%. In total, 78% and 84%, respectively, of the results from the finger prick capillary specimens with the Roche (Accu-Chek Performa meter) and Abbott (Optium Xceed meter) strips, not 95% or greater as recommended by the ISO guideline, were within the recommended limits compared with reference plasma estimation on laboratory analysers. Galactose, ascorbic acid, haematocrit and sodium on the Roche and ascorbic acid and haematocrit on the Abbott strip continue to interfere to a variable degree with the glucose measurement. CONCLUSION: Analytically small differences exist between the glucose meter strips. The most significant analytical difference with the strips was at low glucose levels when compared with laboratory analyses and this may be of clinical importance. The impact of some of the interferences is variable between the two strips. Individuals, health-care professionals and health-care institutions should consider these data when selecting glucose meters for the management of people with diabetes mellitus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to determine the contribution of adipose tissue to the insulin resistance of pregnancy. We also investigated whether hyperosmolar stress (induced by sorbitol) stimulates glucose uptake in human adipose tissue and, if so, whether this effect is altered in pregnancy and gestational diabetes mellitus. STUDY DESIGN: Subcutaneous and omental adipose tissue biopsy specimens were obtained at elective abdominal surgery or cesarean delivery from 16 normal glucose-tolerant pregnant women, 13 pregnant women with gestational diabetes mellitus, and 19 body mass index-matched nonpregnant control subjects. Basal, insulin (100 nmol/L)-, and sorbitol (250 mmol/L)-stimulated glucose uptake levels were measured. RESULTS: Basal and insulin-stimulated glucose uptake into adipose tissue was not impaired in pregnancy or gestational diabetes mellitus compared with control subjects. Hyperosmolarity stimulated glucose uptake in human adipose tissue from the subcutaneous, but not omental depot, and not in adipose tissue from pregnant subjects. CONCLUSION: There is no significant difference in insulin sensitivity in adipose tissue from pregnant or nonpregnant women; hyperosmolarity stimulates glucose uptake in subcutaneous adipose tissue from nonpregnant women, and adipose tissue from pregnant women is sorbitol resistant. These findings suggest the phosphotidylinositol 3-kinase-independent pathway may have pathophysiologic relevance to glucose uptake in human adipose tissue and may be impaired in pregnancy. [ABSTRACT FROM AUTHOR]

Although glycated haemoglobin (HbA(1c)) has become the key biochemical marker of long-term glycaemic control, analytical method-dependent differences in results can occur when haemoglobin variants are present or HbA(1c) is reduced by decreased red cell survival. When the measured HbA(1c) level is discordant with the patient's blood glucose measurements and clinical status, fructosamine is an alternative biochemical marker that can provide a more accurate estimate of the glycaemic control and enable clinicians to appropriately manage patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utilization and costs of non-insulin glucose-lowering drugs (GLDs) in Australia from 2013 to 2023., Materials and Methods: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation., Results: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium-glucose cotransporter-2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon-like peptide-1 receptor agonists (GLP-1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase-4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP-1RAs contributed to 35% of the costs., Conclusion: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP-1RA and SGLT2 inhibitor prescribing., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Global insulin requirements for type 2 diabetes were predicted to increase by more than 20% from 2018 to 2030. However, this did not anticipate the rapid increase in use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors that has occurred over recent years. The current study aims to examine changes in insulin utilisation and costs in Australia from 2003 to 2023., Methods: We conducted a large-scale observational study of national insulin utilisation and expenditure in Australia from 2003 to 2023 using the Australian Pharmaceutical Benefits Scheme. The proportion of insulin-treated people with type 2 diabetes between 2013 and 2023 was estimated using National Diabetes Services Scheme data. Joinpoint models and interrupted time series analysis were used to examine utilisation trends., Findings: Insulin utilisation (units of insulin per person with diabetes) increased by an average of 2.71% per annum (95% CI 1.97, 3.73) from 2003 to 2015, then fell by 2.70% per annum (95% CI -4.55, -1.39) from 2015 to 2023. The proportion of insulin-treated people with type 2 diabetes increased by 1.00% per annum (95% CI 0.81, 1.25) from 2013 to 2020, then fell by 0.66% per annum (95% CI -1.62, -0.04) from 2020 to 2023. A 43% reduction in inflation-adjusted insulin expenditure was observed between 2015 and 2023 due to a combination of reduced utilisation and reduction in the price of insulin glargine., Interpretation: Projected global insulin requirements and costs may be less than previously anticipated if reduced use of insulin in Australia is similarly observed in other countries., Funding: No funding was received for this study., Competing Interests: PSH: Member of the Pharmaceutical Benefits Advisory Committee (PBAC). This work is independent of PBAC and does not reflect the views of PBAC. President-Elect of the Endocrine Society of Australia (ESA). This work is independent of ESA and does not reflect the views of ESA. AE: declares no competing interests. AWR: Speaker Honoraria from Boehringer Ingelheim and Astra Zeneca, paid to a University Research Account; ST: Guest discussant at the Drug Utilisation Subcommittee (DUSC) of PBAC. This work is independent of DUSC and does not reflect the views of DUSC. Grant support from MRFF CVD Mission, paid to Monash University, independent of this work; travel and meeting support from Monash University CCRET, independent of this work. EZ: declares no competing interests. SZ: has received payment to the institution (Monash University) from Eli Lilly Australia, Boehringer-Ingelheim, CSL Sequiris, AstraZeneca, Novo Nordisk, Sanofi and Moderna for consultancy work and travel and accommodation support from Eli Lilly and Novo Nordisk, all independent of this work. Funding from NHMRC, Australian Government—Department of Health and Aged Care, JDRF Centre of Excellence and MRFF, all independent of this work., (© 2024 The Author(s).)

Background: Electronic consultations (eConsults) allow general practitioners (GP) to seek the advice of a specialist via secure asynchronous digital communication., Aims: To report the outcomes of a proof of concept (POC) trial of eConsults for patients with diabetes and endocrine disorders., Methods: A prospective observational study conducted from November 2020 to May 2021. eConsults were provided by endocrinologists from the Princess Alexandra Hospital, Brisbane. The requests for advice were from GP in Brisbane South. An online questionnaire was completed by the GP and endocrinologist after each eConsult., Results: Forty eConsults were performed over 7 months. The majority were in relation to type 2 diabetes (30%) or thyroid conditions (30%). All eConsult responses were performed within the target of 72 h with 92.5% responses provided within 24 h. The average time taken for the endocrinologist to perform the eConsult was 14.2 ± 4.4 min. The GP rated the value of eConsults as excellent 97% of the time. The eConsult resulted in a new or additional course of action 68% (19/28) of the time and confirmed a course of action 32% (9/28) of the time. The eConsult avoided the need for referral of the patient for a face-to-face specialist review in 55% of the eConsults., Conclusion: An eConsult service was able to be delivered by endocrinologists from a tertiary hospital to GP in Brisbane South. With an appropriate funding model, the broader implementation and adoption of eConsults has the potential to address specialist waiting lists and facilitate models of integrated care., (© 2021 Royal Australasian College of Physicians.)

Background: Practice guidelines for coronary heart disease and type 2 diabetes recommend promoting the Mediterranean dietary pattern (MDP), which improves cardiometabolic risk markers and may prevent disease progression and complications. It is unknown to what extent the MDP is recommended in routine care for patients with these conditions, particularly in multiethnic settings., Objective: The study aim was to explore multidisciplinary health care professionals' perspectives on recommending the MDP in routine care for patients with coronary heart disease or type 2 diabetes and barriers and enablers to its implementation., Design: A qualitative description design was employed, utilizing semistructured individual interviews to collect data., Participants and Setting: Fifty-seven clinicians (21 nurses, 19 doctors, 13 dietitians, and 4 physiotherapists) routinely managing relevant patients across hospital and community settings in a metropolitan health service in Australia participated in interviews between November 2019 and March 2020., Statistical Analysis Performed: Interviews were audiorecorded, transcribed verbatim, and analyzed using thematic analysis., Results: Four overarching themes were identified highlighting that the MDP was not routinely recommended: current dietary practices (all clinicians perceived they had a role in dietary care but prioritization varied. There was a legacy of single nutrient-based strategies and disease silos); clinician-centered barriers to recommending MDP (limited MDP knowledge and practice skills and variable understanding and acceptance of evidence supporting its use. This was related to lack of education and training about the diet and personal interest/experience); organizational culture and resources influence dietary care (MDP not embedded in service culture or current clinic tools and resources, with limited dietary knowledge exchange within and across multidisciplinary teams); and perceived patient-centered barriers to implementation of MDP (socioeconomic challenges in a multicultural setting, and a lack of belief in patient capabilities to improve diet adherence)., Conclusions: Clinician and organizational factors, compounded by perceptions about patient acceptance, influence recommendations of the MDP for patients with coronary heart disease or type 2 diabetes. These factors should be addressed to improve translation of MDP evidence into practice., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver-related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB-4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow-up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM > 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5-13 kPa, and in no patients with LSM < 9.5 kPa. No patient with low-risk NFS developed liver decompensation or liver-related mortality. Following repeat NFSs at the end of follow-up, all patients with a liver-related complication were in the high-risk NFS category. Patients who developed liver-related complications were also more likely to have baseline high-risk FIB-4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non-hepatology settings can identify the subset of patients at risk of liver-related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa), these events are projected to lead to a substantial increase in NAFLD-related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Importance: Diabetes is common amongst hospitalised patients and contributes to increased length of stay and poorer outcomes. Digital transformation, particularly the implementation of electronic medical records (EMRs), is rapidly occurring across the healthcare sector and provides an opportunity to improve the safety and quality of inpatient diabetes care. Alongside this revolution has been a considerable and ongoing evolution of digital interventions to optimise care of inpatients with diabetes including optimisation of EMRs, digital clinical decision support systems (CDSS) and solutions utilising data visibility to allow targeted patient review., Objective: To systematically appraise the recent literature to determine which digitally-enabled interventions including EMR, CDSS and data visibility solutions improve the safety and quality of non-critical care inpatient diabetes management., Methods: Pubmed, Embase and Cochrane databases were searched for suitable articles. Selected articles underwent quality assessment and analysis with results grouped by intervention type., Results: 1202 articles were identified with 42 meeting inclusion criteria. Four key interventions were identified; computerised physician order entry (n = 4), clinician decision support systems (n = 21), EMR driven active case finding (data visibility solutions) and targeted patient review (n = 10) and multicomponent system interventions (n = 7). Studies reported on glucometric outcomes, evidence-based medication ordering including medication errors, and patient and user outcomes. An improvement in glucometric measures particularly mean blood glucose and proportion of target range blood glucose levels and rates of evidence-based insulin prescribing were consistently demonstrated., Conclusion: Digitally-enabled interventions utilised to improve quality and safety of inpatient diabetes care were heterogenous in design. The majority of studies across all intervention types reported positive effects for evidence-based prescribing and glucometric outcomes. There was less evidence for digital interventions reducing diabetes medication administration errors or impacting patient outcomes (length of stay)., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Background: There is limited evidence on interventions to minimise weight gain at clozapine commencement. We compared the effect of adjunctive metformin versus placebo at clozapine initiation., Methods: People with schizophrenia commencing on clozapine were randomised to either metformin or placebo for 24 weeks. The primary outcome was difference in the change of body weight. Secondary outcomes included comparative rates of weight gain of more than 5%, overall weight gain/loss, and differences in metabolic and psychosis outcomes., Results: The study was closed prematurely in March 2020 due to COVID-19 restrictions. Ten participants were randomised to each of the metformin and placebo groups. Eight metformin group and five placebo group participants completed the trial and were included in the analysis. The study was insufficiently powered to detect difference between the metformin and placebo groups for the primary outcome of change in weight (0.09 kg vs 2.88 kg, p  = 0.231). In terms of secondary outcomes, people in the metformin group were significantly less likely to gain >5% of their body weight (12.5% vs 80%, p  = 0.015) and were more likely to lose weight (37.5% vs 0% p  = 0.024) compared to placebo. There was no difference between the groups in terms of adverse drug reactions (ADRs)., Conclusion: While limited by the forced premature closure of the trial due to COVID19, the findings from this randomised controlled trial are promising. Clozapine and metformin co-commencement may be a promising treatment to prevent clozapine-associated weight gain, especially given the low rates of ADRs associated with metformin. This supports the consideration of use of metformin to prevent weight gain in people initiated on clozapine; however, further studies are needed to confirm this finding., Trial Registration: ACTRN12617001547336., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2021.)

The COVID-19 pandemic has impacted the management of non-communicable diseases in health systems around the world. This study aimed to understand the impact of COVID-19 on diabetes medicines dispensed in Australia. Publicly available data from Australia's government subsidised medicines program (Pharmaceutical Benefits Scheme), detailing prescriptions by month dispensed to patients, drug item code and patient category, was obtained from January 2016 to November 2020. This study focused on medicines used in diabetes care (Anatomical Therapeutical Chemical code level 2 = A10). Number of prescriptions dispensed were plotted by month at a total level, by insulins and non-insulins, and by patient category (general, concessional). Total number of prescriptions dispensed between January and November of each year were compared. A peak in prescriptions dispensed in March 2020 was identified, an increase of 35% on March 2019, compared to average growth of 7.2% in previous years. Prescriptions dispensed subsequently fell in April and May 2020 to levels below the corresponding months in 2019. These trends were observed across insulins, non-insulins, general and concessional patient categories. The peak and subsequent dip in demand have resulted in a small unexpected overall increase for the period January to November 2020, compared to declining growth for the same months in prior years. The observed change in consumer behaviour prompted by COVID-19 and the resulting public health measures is important to understand in order to improve management of medicines supply during potential future waves of COVID-19 and other pandemics.

Objective This study compared the cost of an integrated primary-secondary care general practitioner (GP)-based Beacon model with usual care at hospital outpatient departments (OPDs) for patients with complex type 2 diabetes. Methods A costing analysis was completed alongside a non-inferiority randomised control trial. Costs were calculated using information from accounting data and interviews with clinic managers. Two OPDs and three GP-based Beacon practices participated. In the Beacon practices, GPs with a special interest in advanced diabetes care worked with an endocrinologist and diabetes nurse educator to care for referred patients. The main outcome was incremental cost saving per patient course of treatment from a health system perspective. Uncertainty was characterised with probabilistic sensitivity analysis using Monte Carlo simulation. Results The Beacon model is cost saving: the incremental cost saving per patient was A$365 (95% confidence interval -A$901, A$55) and was cost saving in 93.7% of simulations. The key contributors to the variance in the cost saving per patient course of treatment were the mean number of patients seen per site and the number of additional presentations per course of treatment associated with the Beacon model. Conclusions Beacon clinics were less costly per patient course of treatment than usual care in hospital OPDs for equivalent clinical outcomes. Local contractual arrangements and potential variation in the operational cost structure are of significant consideration in determining the cost-efficiency of Beacon models. What is known about this topic? Despite the growing importance of achieving care quality within constrained budgets, there are few costing studies comparing clinically-equivalent hospital and community-based care models. What does this paper add? Costing analyses comparing hospital-based to GP-based health services require considerable effort and are complex. We show that GP-based Beacon clinics for patients with complex chronic disease can be less costly per patient course of treatment than usual care offered in hospital OPDs. What are the implications for practitioners? In addition to improving access and convenience for patients, transferring care from hospital to the community can reduce health system costs.

Background: Incomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion., Methods: The MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length., Results: Experiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02)., Conclusions: Presence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF)., Methods: We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater., Results: Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log 10 FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52-0.59). The rate of increase in NFS and log 10 FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log 10 FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively., Conclusions: Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Hyponatraemia in hospitalized patients is common and associated with increased mortality. International guidelines give conflicting advice regarding the role of urea in the treatment of SIADH. We hypothesized that urea is a safe, effective treatment for fluid restriction-refractory hyponatraemia., Design: Review of urea for the treatment of hyponatraemia in patients admitted to a tertiary hospital during 2016-2017. Primary end-point: proportion of patients achieving a serum sodium ≥130 mmol/L at 72 hours., Patients: Urea was used on 78 occasions in 69 patients. The median age was 67 (IQR 52-76), 41% were female. Seventy (89.7%) had hyponatraemia due to SIADH-CNS pathology (64.3%) was the most common cause. The duration was acute in 32 (41%), chronic in 35 (44.9%) and unknown in the rest., Results: The median nadir serum sodium was 122 mmol/L (IQR 118-126). Fluid restriction was first-line treatment in 65.4%. Urea was used first line in 21.8% and second line in 78.2%. Fifty treatment episodes (64.1%) resulted in serum sodium ≥130 mmol/L at 72 hours. In 56 patients who received other prior treatment, the mean sodium change at 72 hours (6.9 ± 4.8 mmol/L) was greater than with the preceding treatments (-1.0 ± 4.7 mmol/L; P < 0.001). Seventeen patients (22.7%) had side effects (principally distaste), none were severe. No patients developed hypernatraemia, overcorrection (>10 mmol/L in 24 hours or >18 mmol/L in 48 hours), or died., Conclusions: Urea is safe and effective in fluid restriction-refractory hyponatraemia. We recommend urea with a starting dose of ≥30 g/d, in patients with SIADH and moderate to profound hyponatraemia who are unable to undergo, or have failed fluid restriction., (© 2019 John Wiley & Sons Ltd.)

Aims: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls., Materials and Methods: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP-1RA)'. Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent., Results: Three studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly impact outcomes. Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001). Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8)., Conclusion: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs., (© 2018 John Wiley & Sons Ltd.)

Aims/hypothesis: The aim of the study was to determine if a Beacon model of integrated care utilising general practitioners (GPs) with special interests could achieve similar clinical outcomes to a hospital-based specialist diabetes outpatient clinic., Methods: This pragmatic non-inferiority multisite randomised controlled trial assigned individuals with complex type 2 diabetes to care delivered by a Beacon clinic or to usual care delivered by a hospital outpatient department, in a 3:1 ratio. Owing to the nature of the study, researchers were only blinded during the allocation process. Eligible participants were aged 18 or over, had been referred by their usual GP to the hospital central referral hub with type 2 diabetes and had been triaged to be seen within 30 or 90 days. The intervention consisted of diabetes management in primary care by GPs with a special interest who had been upskilled in complex diabetes under the supervision of an endocrinologist. The primary outcome was HbA 1c at 12 months post-recruitment. The non-inferiority margin was 4.4 mmol/mol (0.4%). Both per-protocol and intention-to-treat analyses are reported., Results: Between 27 November 2012 and 14 July 2015, 352 individuals were recruited and 305 comprised the intention-to-treat sample (71 in usual care group and 234 in the Beacon model group). The Beacon model was non-inferior to usual care for both the per-protocol (difference -0.38 mmol/mol [95% CI -4.72, 3.96]; -0.03% [95% CI -0.43, 0.36]) and the intention-to-treat (difference -1.28 mmol/mol [95% CI -5.96, 3.40]; -0.12% [95% CI -0.55, 0.31]) analyses. Non-inferiority was sustained in a sensitivity analysis at 12 months. There were no statistically or clinically significant differences in the secondary outcomes of BP, lipids or quality of life as measured by the 12 item short-form health survey (SF-12v2) and the diabetes-related quality of life (DQoL-Brief) survey. Safety indicators did not differ between groups. Participant satisfaction on the eight-item client satisfaction questionnaire (CSQ-8) was good in both groups, but scores were significantly higher in the Beacon model group than the usual care group (mean [SD] 28.4 [4.9] vs 25.6 [4.9], respectively, p < 0.001)., Conclusions/interpretation: In individuals with type 2 diabetes, a model of integrated care delivered in the community by GPs with a special interest can safely achieve clinical outcomes that are not inferior to those achieved with gold-standard hospital-based specialist outpatient clinics. Individuals receiving care in the community had greater satisfaction. Further studies will determine the cost of delivering this model of care., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12612000380897 FUNDING: The study was funded by the Australian National Health and Medical Research Council (GNT1001157).

Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are recommended as first-line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m 2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB-4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB-4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06-1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01-1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. ( Hepatology Communications 2018; 00:000-000).

Aims: To examine the relationship between steatosis quantified by controlled attenuation parameter (CAP) values and glycaemic/metabolic control., Methods: 230 patients, recruited from an Endocrine clinic or primary care underwent routine Hepatology assessment, with liver stiffness measurements and simultaneous CAP. Multivariable logistic regression was performed to identify potential predictors of Metabolic Syndrome (MetS), HbA1c ≥ 7%, use of insulin, hypertriglyceridaemia and CAP ≥ 300 dB/m., Results: Patients were 56.7 ± 12.3 years of age with a high prevalence of MetS (83.5%), T2DM (81.3%), and BMI ≥ 40 kg/m 2 (18%). Median CAP score was 344 dB/m, ranging from 128 to 400 dB/m. BMI (aOR 1.140 95% CI 1.068-1.216), requirement for insulin (aOR 2.599 95% CI 1.212-5.575), and serum ALT (aOR 1.018 95% CI 1.004-1.033) were independently associated with CAP ≥ 300 dB/m. Patients with CAP interquartile range < 40 (68%) had a higher median serum ALT level (p = 0.029), greater prevalence of BMI ≥ 40 kg/m 2 (p = 0.020) and higher median CAP score (p < 0.001). Patients with higher CAP scores were more likely to have MetS (aOR 1.011 95% CI 1.003-1.019), HBA1c ≥ 7 (aOR 1.010 95% CI 1.003-1.016), requirement for insulin (aOR 1.007 95% CI 1.002-1.013) and hypertriglyceridemia (aOR 1.007 95% CI 1.002-1.013)., Conclusions: Our data demonstrate that an elevated CAP reflects suboptimal metabolic control. In diabetic patients with NAFLD, CAP may be a useful point-of-care test to identify patients at risk of poorly controlled metabolic comorbidities or advanced diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Many patients with diabetes require insulin therapy to achieve optimal glycemic control. Initiation and titration of insulin often require an insulin dose adjustment (IDA) program, involving frequent exchange of blood glucose levels (BGLs) and insulin prescription advice between the patient and healthcare team. This process is time consuming with logistical barriers., Objective: To develop an innovative mobile health (m-Health) mobile-based IDA program (mIDA) and evaluate the user adherence and experience through a proof-of-concept trial., Methods: In the program, an m-Health system was designed to be integrated within a clinical IDA service, comprising a Bluetooth-enabled glucose meter, smartphone application, and clinician portal. Insulin-requiring patients with type-2 diabetes mellitus and stable BGL were recruited to use the m-Health system to record and exchange BGL entries, insulin dosages, and clinical messages for 2 weeks. The user experience was evaluated by a Likert scale questionnaire., Results: Nine participants, aged 58 ± 14 years (mean ± SD), completed the trial with average daily records of 3.1 BGL entries and 1.2 insulin dosage entries. The participants recognized the potential value of the clinical messages. They felt confident about managing their diabetes and were positive regarding ease of use and family support of the system, but disagreed that there were no technical issues. Finally, they were satisfied with the program and would continue to use it if possible., Conclusions: The m-Health system for IDA showed promising levels of adherence, usability, perception of usefulness, and satisfaction. Further research is required to assess the feasibility and cost-effectiveness of using this system in outpatient settings.

This case study describes the development and implementation of an innovative integrated primary-secondary model of care for people with complex diabetes. The aim of the paper is to present the experiences of clinicians and researchers involved in implementing the 'Beacon' model by providing a discussion of the contextual factors, including lessons learned, challenges and solutions. Beacon-type models of community care for people with chronic disease are well placed to deliver on Australia's health care reform agenda, and this commentary provides rich contextual information relevant to the translation of such models into policy and practice.

Clozapine causes obesity and type 2 diabetes (T2DM). Glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomized, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. A total of 28 outpatients were randomized to once-weekly extended-release subcutaneous exenatide or usual care for 24 weeks. The primary outcome was proportion of participants with >5% weight loss. All 28 participants completed the study; 3/14 in the exenatide group and 2/14 in the usual care group had T2DM. Six people on exenatide achieved >5% weight loss vs one receiving usual care (P = .029). Compared with usual care, participants on exenatide had greater mean weight loss (-5.29 vs -1.12 kg; P = .015) and body mass index reduction (-1.78 vs -0.39 kg/m 2 ; P = .019), and reduced fasting glucose (-0.34 vs 0.39 mmol/L; P = .036) and glycated haemoglobin levels (-0.21% vs 0.03%; P = .004). There were no significant differences in other metabolic syndrome components. Exenatide may be a promising therapeutic agent for glycaemic control and weight loss in clozapine-treated people with obesity, and could assist in reducing clozapine-associated cardio-metabolic morbidity and mortality., (© 2017 John Wiley & Sons Ltd.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis., Aim: To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD., Methods: A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected., Results: A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal., Conclusion: Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed., (© 2017 Royal Australasian College of Physicians.)

Aims: To investigate the role of ophthalmic imaging markers - namely retinal thickness measures and corneal nerve morphology - in predicting four-year development and worsening of diabetic retinopathy (DR) in type 1 diabetes (T1DM)., Methods: 126 eyes of 126 participants with T1DM were examined at baseline and after four years. Diabetic retinopathy (DR) was graded using the Early Treatment Diabetic Retinopathy Study scale. HbA 1c , nephropathy, neuropathy, cardiovascular factors, and retinal thickness using optical coherence tomography (OCT) and corneal nerve fiber length (CNFL) using corneal confocal microscopy at baseline were assessed by univariate and step-wise multiple logistic regression, and their diagnostic capabilities for single and combined measures., Results: Four-year development of DR was 19% (13 of 68 without DR at baseline). Worsening of DR was seen in 43% (25 of 58 with DR at baseline). When adjusted for potential confounders, a lower CNFL (AUC=0.637, p=0.040, 64% sensitivity and 64% specificity at 14.9mm/mm 2 cut-off), higher triglycerides (AUC=0.669, p=0.012, 64% sensitivity, 62% specificity at 0.85mmol/L) and an elevated vibration threshold (AUC=0.708, p=0.002, 96% sensitivity, 40% specificity at 3.55Hz) were significant predictors for four-year worsening of DR., Conclusions: Reduced CNFL, elevated vibration perception threshold and higher triglycerides can predict future worsening of DR., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow-up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management., Design and Patients: A single-centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years. Serial tumour images were analysed for size, location and growth rate (GR) and tissue analysed for hormone cell type and proliferation indices with secondary treatment as outcome measure., Results: Twenty-four of 66 (36%) patients harbouring a postoperative remnant required secondary treatment, all occurring within 10 years. No secondary treatment was required in any of 42 patients with complete tumour resection. Age, gender, remnant volume and tumour histology were not different between patients requiring and not requiring secondary therapy. Remnant GRs in those requiring secondary therapy were more than 10-fold higher (P<.01). Tumours with a GR ≥80 mm 3 /y (Hazard Ratio[HR]: 8.1, Confidence Interval [CI]: 2.4-27.3,P<.01) and those located in the suprasellar region (HR: 6.1, CI: 1.1-32, P=.03) had a higher risk for secondary therapy. Tumour GR in the first three postoperative years correlated significantly (r 2 =.6, P<.01) with GR during the period of follow-up., Conclusion: In surgically resected NFAs further treatment is dependent on the presence of residual tumour, growth rate and location but not tumour histology. Postoperative growth rate of NFAs in the first 3 years of imaging can be used to tailor long-term follow-up to optimize use of health resources., (© 2017 John Wiley & Sons Ltd.)

Purpose: To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR)., Methods: Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined., Results: The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups., Conclusions: Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

This study aimed to describe patient-related characteristics of those attending the diabetes telehealth service delivered from a tertiary hospital and compare these with the characteristics of patients attending face-to-face visits at the same hospital's diabetes outpatient service. This analysis could inform diabetes telehealth service improvements. To our knowledge, there has been no prior evaluation of a diabetes telehealth service in Australia. A cross-sectional survey was conducted as part of the Australian National Diabetes Audit in May 2016 for all patients attending the diabetes telehealth service and diabetes outpatient service. The diabetes telehealth service was serving a greater proportion of females, indigenous people and patients with a longer mean duration of type 2 diabetes mellitus. Type 2 diabetes mellitus patients in the diabetes telehealth service group had a higher average glycated haemoglobin of 9.1% (76 mmol/mol) vs 8.1% (65 mmol/mol) in the diabetes outpatient service group. The diabetes telehealth service had more people with initial visits; had higher self-reported smoking rates in type 2 diabetes mellitus patients; and had adequate access to allied health supports as recommended for diabetes management. Diabetes telehealth service patients had more complex diabetes as evidenced by a higher proportion of indigenous clients, higher glycated haemoglobin and longer mean duration of diabetes.

Purpose: To examine the diagnostic capability of the full retinal and inner retinal thickness measures in differentiating individuals with diabetic peripheral neuropathy (DPN) from those without neuropathy and non-diabetic controls., Methods: Individuals with (n=44) and without (n=107) diabetic neuropathy and non-diabetic control (n=42) participants underwent spectral domain optical coherence tomography (SDOCT). Retinal thickness in the central 1mm zone (including the fovea), parafovea and perifovea was assessed in addition to ganglion cell complex (GCC) global loss volume (GCC GLV) and focal loss volume (GCC FLV), and retinal nerve fiber layer (RNFL) thickness. Diabetic neuropathy was defined using a modified neuropathy disability score (NDS) recorded on a 0-10 scale, wherein, NDS ≥3 indicated neuropathy and NDS indicated <3 no neuropathy. Diagnostic performance was assessed by areas under the receiver operating characteristic curves (AUCs), 95 per cent confidence intervals (CI), sensitivities at fixed specificities, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the cut-off points for the best AUCs obtained., Results: The AUC for GCC FLV was 0.732 (95% CI: 0.624-0.840, p<0.001) with a sensitivity of 53% and specificity of 80% for differentiating DPN from controls. Evaluation of the LRs showed that GCC FLV was associated with only small effects on the post-test probability of the disease. The cut-off point calculated using the Youden index was 0.48% (67% sensitivity and 73% specificity) for GCC FLV. For distinguishing those with neuropathy from those without neuropathy, the AUCs of retinal parameters ranged from 0.508 for the central zone to 0.690 for the inferior RNFL thickness. For distinguishing those with moderate or advanced neuropathy from those with mild or no neuropathy, the inferior RNFL thickness demonstrated the highest AUC of 0.820, (95% CI: 0.731-0.909, p<0.001) with a sensitivity of 69% and 80% specificity. The cut-off-point for the inferior RNFL thickness was 97μm, with 81% sensitivity and 72% specificity., Conclusions: The GCC FLV can differentiate individuals with diabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be required to identify patients with minimal neuropathy., (Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To examine the capability of optical coherence tomography-derived retinal thickness measures in detecting 4-year incident diabetic peripheral neuropathy (DPN)., Methods: 145 eyes of 145 participants with diabetes but no DPN at baseline were examined for incident DPN. HbA 1c levels, nephropathy, neuropathy (DPN), cardiovascular measures, and various retinal thickness measures were examined at baseline and after 4 years. Incidence of DPN was defined as newly developed DPN at follow-up. Baseline factors were assessed by univariate and a step-wise multiple logistic regression, and the predictors were examined for diagnostic capabilities., Results: Of the 145 participants without DPN at baseline, 51 had developed DPN when examined after 4 years (35% incidence). Of the ophthalmic variables, the mean (S.D.) of the overall thickness in the parafovea at baseline was 315 (18) μm in the no DPN group and 306 (18) μm in the 'incidence' group, and the differences were significant, p = 0.005. The superior hemisphere parafovea (mean (S.D.): 318 (17) μm vs 310 (20) μm, p = 0.02) and inferior hemisphere parafovea (313 (19) μm vs 302 (18) μm, p = 0.002) were different in the incident DPN group compared with the no DPN group. When adjusted for age, retinal thickness in the parafovea (AUC = 0.65, p = 0.003, 86% sensitivity and 44% specificity at 321 μm criterion), and body mass index or BMI (AUC = 0.65, p = 0.003, 49% sensitivity and 83% specificity at 29.3 kg m -2 criterion) at baseline were significant predictors for 4-year incident DPN., Conclusions: A lower retinal thickness at the parafovea and a higher BMI can predict 4-year incident neuropathy in patients with diabetes, with acceptable diagnostic accuracies. This OCT-derived measure may serve as a potential ophthalmic marker in the screening of patients at risk of developing DPN., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

An observational study describing the number and type of chronic conditions and medications taken by diabetic patients with NAFLD and identifying characteristics that may impact liver disease severity or clinical management.Adults with type 2 diabetes have a high prevalence of nonalcoholic fatty liver disease (NAFLD) and increased risk of developing advanced liver disease. Appropriate management should consider the characteristics of the diabetic NAFLD population, as comorbid conditions and medications may increase the complexity of treatment strategies.Diabetic patients with NAFLD at risk of clinically significant liver disease (as assessed by the FIB-4 or NAFLD fibrosis scores) were recruited consecutively from the Endocrine clinic or primary care. Medical conditions, medication history, anthropometric measurements, and laboratory tests were obtained during assessment. NAFLD severity was classified by transient elastography and liver ultrasound into "no advanced disease" (LSM < 8.2 kPa) or "clinically significant liver disease" (LSM ≥ 8.2 kPa).The most common coexistent chronic conditions were metabolic syndrome (94%), self-reported "depression" (44%), ischaemic heart disease (32%), and obstructive sleep apnoea (32%). Polypharmacy or hyperpolypharmacy was present in 59% and 31% of patients respectively. Elevated LSM (≥ 8.2 kPa) suggesting significant liver disease was present in 37% of this at-risk cohort. Increasing obesity and abdominal girth were both independently associated with likelihood of having significant liver disease.There is a high burden of multimorbidity and polypharmacy in diabetic NAFLD patients, highlighting the importance of multidisciplinary management to address their complex health care needs and ensure optimal medical treatment.

As the prevalence of type 2 diabetes continues to escalate, health system reform is seeking better patient outcomes through new models of care that aim to provide the most appropriate care when needed. Patients' experiences of service innovations can shed light on the successes and challenges of implementing change. This paper explores patients' views of a new model of integrated care for patients with type 2 diabetes. A mixed-methods, randomised control trial evaluated a beacon clinic model of care for complex type 2 diabetes led by specialist general practitioners (GPs) in primary care settings in Brisbane, Australia. In this qualitative sub-study conducted between May 2014 and January 2015, 25 consenting participants were re-interviewed after 12 months using semi-structured questions, to explore their experiences of the new model of care. Interview transcripts were analysed thematically. In the first theme, Organised for patient-centred care, patients appraised the structural elements of the clinic. For most, it was an enabling experience which included convenience, flexibility and prompt communication back to the referring GPs. The preferences of a minority were partly realised, as they tried to understand the clinical purpose in comparison with traditional care. The second theme, Positioned as partners in care, revealed the pivotal role of patient-clinician relationships in patients' engagement with advice and self-care. Most found clinicians' collaborative approach engaging and motivating. A small minority with contextual concerns were disappointed with the focus on diabetes and struggled to engage fully with the model. Most participants valued this model of care, which reflects a capacity to manage the variable and complex needs of most patients referred for care. However, multi-level strategies are also needed to enhance patients' engagement with care and the sustainability of integrated diabetes care., (© 2016 John Wiley & Sons Ltd.)

Purpose: Reduced retinal nerve fiber layer (RNFL) thickness has been demonstrated in patients with diabetic peripheral neuropathy (DPN) in cross-sectional studies. This prospective study defines longitudinal alterations to the RNFL thickness in individuals with type 1 diabetes without (DPN-ve) and with (DPN+ve) DPN and in relation to risk factors for nerve damage., Methods: A cohort of 105 individuals with type 1 diabetes (20% DPN+ve) with predominantly mild or no retinopathy and no previous retinal photocoagulation underwent spectral-domain optical coherence tomography (SD-OCT) at baseline, 2 years, and 4 years. SD-OCT scans were acquired at 3.45-mm diameter around the optic nerve head and the overall RNFL and RNFL in the nasal, superior, temporal, and inferior quadrants were quantified. By including serial quantified RNFL parameters, linear mixed models were applied to assess the change in RNFL thickness over time and to explore the associations with other clinical variables., Results: There was a significant decline in the overall RNFL thickness (-0.7 μm/y, P = 0.02) and RNFL in the superior quadrant (-1.9 μm/y, P < 0.01) in the DPN+ve group compared with DPN-ve group. The overall RNFL thickness and RNFL in the superior and nasal quadrants were inversely associated with age (β = -0.29, -0.41, and -0.29, respectively; P ≤ 0.02). Sex, retinopathy, diabetes duration, hemoglobin A1c, lipid profile, blood pressure, cigarette use, alcohol consumption, and body mass index did not show any significant effects (P > 0.05)., Conclusions: Individuals with DPN showed a progressive RNFL thinning overall and in the superior quadrant, which was more pronounced in older individuals. There may be common pathways for retinal and peripheral neurodegeneration that are independent of conventional DPN risk factors.

Aim: To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD., Methods: A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day)., Result: Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male ( p = 0.008) and to be Caucasian ( p = 0.007) and to have a history of cigarette smoking ( p = 0.000), obstructive sleep apnea ( p = 0.003), and self-reported depression ( p = 0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control ( p = 0.041) and fibrate medication to lower blood triglyceride levels ( p = 0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67-4.82; p = 0.247) and moderate drinkers had 0.91 (95% CI: 0.27-3.10; p = 0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index)., Conclusions: In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.

Background: The aim was to investigate the relationship between diabetic peripheral neuropathy (DPN) and abnormalities in ganglion cell complex (GCC); specifically, focal loss volume (FLV) and global loss volume (GLV)., Methods: The ganglion cell complex was evaluated using optical coherence tomography on 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes and 42 without diabetes). In those with diabetes, 88 had diabetes but no diabetic retinopathy (no DR group) and 63 had diabetes with diabetic retinopathy (DR group). Seventeen individuals in the no DR group and 27 in the DR group had diabetic peripheral neuropathy according to the neuropathy disability score (NDS). The probability of FLV and GLV being abnormal was determined. Forty four individuals had diabetic peripheral neuropathy (NDS of three or greater). Binary logistic regression analysis was performed, adjusting for the presence of diabetic retinopathy, age, sex, type of diabetes, duration of diabetes and HbA 1c levels., Results: Twenty-five per cent of individuals with diabetic peripheral neuropathy had abnormal FLV compared to 11 per cent of those with diabetes but no diabetic peripheral neuropathy and five per cent in the control group (p = 0.011). Fourteen per cent of individuals with diabetic peripheral neuropathy, 10 per cent without diabetic peripheral neuropathy and two per cent in the control group had abnormal GLV (p = 0.185). For every unit increase in the neuropathy disability score, the odds of having an abnormal FLV increased by a factor of 1.25 (p = 0.007), after adjusting for potentially confounding factors. Abnormal GCC FLV is an independent predictor of diabetic neuropathy, (odds ratio = 2.94, 95 per cent CI [1.16, 7.40], p = 0.023)., Conclusion: Diabetic peripheral neuropathy is associated with abnormal GCC FLV at the macula, which is independent of diabetic retinopathy, age, sex, type of diabetes, duration of diabetes and HbA 1c levels. An abnormality in GCC FLV is an independent predictor of diabetic peripheral neuropathy., (© 2016 Optometry Australia.)

We present clinical, neuropathy and corneal nerve morphology data in a participant with type 2 diabetes who developed diabetic foot ulceration, partial amputation and Charcot during a longitudinal observational study. While conventional measures of neuropathy did not deteriorate significantly, corneal nerve parameters showed a rapid reduction prior to the development of foot complications., Competing Interests: The authors report no conflicts of interest related to this article, (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To assess if diabetes alters corneal epithelial, anterior stromal and subbasal nerve plexus morphology and to determine the associations between these and other clinical variables., Methods: A cohort of 78 participants with diabetes (39 with Type 1 and 39 with Type 2 diabetes) and 29 age-matched healthy controls underwent laser-scanning confocal microscopy of the central cornea. Intermediate cell density (ICD), basal cell density (BCD), anterior stromal cell density (ASCD), corneal nerve fiber density (CNFD) and nerve fiber length (CNFL) were quantified., Results: Compared with controls, participants with diabetes showed reduced ICD (6097 ± 669 vs. 5548 ± 669 no/mm 2 , P<.01), BCD (8925 ± 1196 vs. 7842 ± 1040 cell/mm 2 , P<.01), CNFD (23.4 ± 9.1 vs. 17.5 ± 9.7 no/mm 2 , P<.01) and CNFL (21.0 ± 4.0 vs. 17.4 ± 4.9 mm/mm 2 , P<.01), with no difference in ASCD (785 ± 262 vs. 733 ± 278 cell/mm 2 , respectively, P=.40). None of these structural parameters were associated with type of diabetes (P>.06). Multiple regression analysis showed that ICD and BCD were inversely associated with the diabetes duration and diastolic blood pressure (P<.05) and positively associated with CNFD (P<.01). CNFD and CNFL were inversely associated with HbA 1c (P<.01), while ASCD was inversely associated with age (P<.01)., Conclusions: Corneal epithelial cells and subbasal nerve fibers are reduced in patients with diabetes; however, anterior stromal cells show no difference. Furthermore, abnormalities in corneal epithelial cells and nerves are interrelated and correlated with modifiable risk factors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness., Methods: Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA 1c levels., Results: In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA 1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04)., Conclusions: DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.

Background: Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine., Methods: We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers., Results: Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results., Conclusions: Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered., Trial Registration: PROSPERO registration number: CRD42015029723.

Purpose: The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over 4 years using in vivo corneal confocal microscopy in participants with type 1 diabetes and to identify significant risk factors associated with these alterations., Methods: A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning in vivo corneal confocal microscopy, ocular screening, and health and metabolic assessment at baseline, and the examinations continued for 4 subsequent annual visits. At each annual visit, 8 central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density, corneal nerve branch density and corneal nerve fiber length. Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters., Results: A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure, or body mass index. However, corneal nerve fiber density was negatively associated with glycated hemoglobin (β = -0.76, P < 0.01) and age (β = -0.13, P < 0.01) and positively related to high-density lipids (β = 2.01, P = 0.03). Higher glycated hemoglobin (β = -1.58, P = 0.04) and age (β = -0.23, P < 0.01) also negatively impacted corneal nerve branch density. Corneal nerve fiber length was only affected by higher age (β = -0.06, P < 0.01)., Conclusions: Glycemic control, high-density lipid, and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage and the capability of in vivo corneal confocal microscopy for monitoring subclinical alterations in the corneal SNP in diabetes.

Purpose: To examine the retinal thickness profiles of individuals with and without diabetic retinopathy (DR)., Methods: Full retinal thickness in the central zone, overall and hemisphere thicknesses of the parafovea and perifovea, ganglion cell complex (GCC) thickness and retinal nerve fibre layer (RNFL) thickness were assessed in 185 individuals using spectral domain optical coherence tomography (88 individuals with diabetes but no DR, 55 with DR, and 42 non-diabetic controls). The DR group comprised of 60% of participants with very mild non-proliferative diabetic retinopathy (NPDR) (representing microaneurysms only) and 40% with mild NPDR (hard exudates, cotton-wool spots, and/or mild retinal haemorrhages). Regression analysis was performed to determine the factors associated with retinal tissue thickness, taking into account, age, sex, presence of DR, duration of diabetes, HbA1c levels and type of diabetes., Results: The mean (S.D.) of the overall parafoveal thickness was 306 (16) in the DR group and 314 (14) in the control group (p = 0.02). The mean (S.D.) of the superior hemisphere parafoveal thickness was 309 (16) in the DR group and 318 (14) in the control group (p = 0.02). The mean (S.D.) of the inferior hemisphere parafoveal thickness was 303 (17) in the DR group and 311 (15) in the control group (p = 0.02). There were no significant differences in retinal thickness between groups in the central zone (p = 0.27) or perifovea (p > 0.41). Neither the overall nor the hemisphere RNFL (p > 0.75) and GCC thickness (p > 0.37) were significantly different between the groups. Regression analysis revealed that parafoveal thickness in diabetic individuals was reduced in association with presence of DR (B = -5.9 μm, p = 0.02) and with advancing age (B = -4.5 μm, p = 0.004, for every 10 year increase in age) when adjusted for sex, duration of diabetes, HbA1c levels and type of diabetes., Conclusion: The inner macula is thinner in the presence of clinical signs of diabetic retinopathy and is compounded by advancing age. The influence of any macular oedema or that by cotton-wool spots could not be ruled out and may still confound these results., (© 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.)

Clozapine is the most effective antipsychotic, but its use is tempered by adverse metabolic effects such as weight gain, glucose intolerance and type II diabetes. Current interventions do not facilitate compelling or sustained improvement in metabolic status. Recent studies suggest that glucagon-like peptide-1 (GLP-1) may play a key role in clozapine's metabolic effects, possibly suggesting that clozapine-associated obesity and diabetes are mediated independently through reduced GLP-1. As a result, GLP-1 agonists could show promise in reversing antipsychotic-induced metabolic derangements, providing mechanistic justification that they may represent a novel approach to treat, and ultimately prevent, both diabetes and obesity in patients on clozapine. GLP-1 agonists are already used for diabetes, and they provide a unique combination of glycaemic improvement and metabolically relevant weight loss in diabetic and non-diabetic patients, in the context of a currently favourable safety profile. Using GLP-1 agonists for clozapine-associated obesity and diabetes could be a potentially effective intervention that may reduce cardiometabolic morbidity and mortality in this vulnerable patient population., (© The Author(s) 2016.)