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Less than 20% of Australians with type 1 diabetes (T1D) meet recommended glucose targets. Technology use is associated with better glycaemia, with the most advanced being automated insulin delivery (AID) systems, which are now recommended as gold-standard T1D care. Our Australian AID trial shows a wide spectrum of adults with T1D can achieve recommended targets. Other studies, including lived experience data, are supportive. Insulin pumps are not subsidised for most Australian adults with T1D. We advocate change., (© 2024 Royal Australasian College of Physicians.)

Background: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use., Aims: To investigate glycaemic control and other clinical outcomes in people with type 2 diabetes (T2D) treated with IDegAsp in a real-world setting in Australia., Methods: A total of 183 adults with T2D initiating or switching to IDegAsp in the Australian cohort of the open-label, non-interventional ARISE study were followed for 26-36 weeks from August 2019 to December 2020., Results: IDegAsp was associated with significant reductions from baseline to end of study (EOS) in mean glycated haemoglobin (estimated change -0.8% (95% confidence interval (CI): -1.05 to -0.56; P < 0.0001)), fasting plasma glucose (-1.6 mmol/L (95% CI: -2.49 to -0.63; P = 0.0017)) and body weight (-2.6 kg (95% CI: -3.68 to -1.55; P < 0.0001)). In insulin-experienced patients, the mean total daily insulin dose did not change significantly (estimated change from baseline to EOS 3.8 (95% CI: -3.70 to 11.21; P = 0.3202)). The proportion of patients experiencing hypoglycaemia numerically decreased during the study (non-severe: 14.2-10.9%; nocturnal non-severe: 4.9-2.2%; and severe: 2.2-0%)., Conclusions: Initiating or switching to IDegAsp in a real-world population of people with T2D in Australia was associated with significant improvements in glycaemic control and body weight, and numerically lower levels of hypoglycaemia compared with baseline., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

There have been shortages of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for type 2 diabetes (T2D) care. Analyses of data from 811 T2D adults at an Australian specialist diabetes clinic (1/2019-10/2023) who received ≥ 2 GLP-1 RA prescriptions before and during the shortage showed median HbA1c levels significantly increased by 0.3 %., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [These authors disclose the following: NN has received honoraria/participated a Data Safety Monitoring Board or Advisory Board from Lilly, MH has received Support for attending meetings and/or travel from JDRF Australia and is Associate Editor of Bioscience Reports, AJ is Chair Elect IDF Western Pacific Region, Insulin For Life Global and Australia Board Member NC has received honoraria for lectures from Lectures Novo Nordisk, Lilly, Astra Zeneca, participated a Data Safety Monitoring Board or Advisory Board for Lilly.]., (Copyright © 2024. Published by Elsevier B.V.)

Aims: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities., Methods: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120)., Results: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α  = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: r s  = -0.57) and treatment satisfaction (DTSQ; r s  = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: r s  = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy., Conclusions: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: Multiple automated insulin delivery (AID) systems have become commercially available following randomised controlled trials demonstrating benefits in people with type 1 diabetes (T1D). However, their real-world utility may be undermined by user-associated burdens, including the need to carbohydrate count and deliver manual insulin boluses. There is an important need for a 'fully automated closed loop' (FCL) AID system, without manual mealtime boluses. The (Closed Loop Open SourcE In Type 1 diabetes) trial is a randomised trial comparing an FCL AID system to the same system used as a hybrid closed loop (HCL) in people with T1D, in an outpatient setting over an extended time frame., Methods and Analysis: Randomised, open-label, parallel, non-inferiority trial comparing the Android Artificial Pancreas System (AAPS) AID algorithm used as FCL to the same algorithm used as HCL. Seventy-five participants aged 18-70 will be randomised (1:1) to one of two treatment arms for 12 weeks: (a) FCL-participants will be advised not to bolus for meals and (b) HCL-participants will use the AAPS AID algorithm as HCL with announced meals. The primary outcome is the percentage of time in target sensor glucose range (3.9-10.0 mmol/L). Secondary outcomes include other glycaemic metrics, safety, psychosocial factors, platform performance and user dietary factors. Twenty FCL arm participants will participate in a 4-week extension phase comparing glycaemic and dietary outcomes using NovoRapid (insulin aspart) to Fiasp (insulin aspart and niacinamide)., Ethics and Dissemination: Approvals are by the Alfred Health Ethics Committee (615/22) (Australia) and Health and Disability Ethics Committees (2022 FULL 13832) (New Zealand). Each participant will provide written informed consent. Data protection and confidentiality will be ensured. Study results will be disseminated by publications, conferences and patient advocacy groups., Trial Registration Numbers: ACTRN12622001400752 and ACTRN12622001401741., Competing Interests: Competing interests: TW, DT, EB, YE and NN have nothing to disclose. MdB declares receiving speaker fees from Medtronic, Dexcom, Boerhinger Ingelheim, research support from Dexcom, Medtronic, Novonordisk, Pfizer, SOOIL, and has served as advisory board membership for Dexcom. NDC declares speaker fees from Novo Nordisk, Lilly, Boehringer Ingelheim, Abbott and research support from Ypsomed, Novo Nordisk, Boehringer Ingelheim, Astra Zeneca, Novartis. JW declares research support from Dexcom and SOOIL. DB declares employment at Nascence Biomed (which provides the technical platform for the CLOSE IT trial) and serving on an editorial board for Ascensia., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway., Method: An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure., Intervention: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure., Results: The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio)., Conclusions: The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose, (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n  = 436). Thirteen drivers recorded at least one trip (total n  = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Background & Aims: Whether the frequency of interruptions to sitting time involving simple resistance activities (SRAs), compared to uninterrupted sitting, differentially affected 22 h glycemic control in adults with medication-controlled type 2 diabetes (T2D)., Methods & Results: Twenty-four participants (13 men; mean ± SD age 62 ± 8 years) completed three 8 h laboratory conditions: SIT: uninterrupted sitting; SRA3: sitting interrupted with 3 min of SRAs every 30 min; and, SRA6: sitting interrupted with 6 min of SRAs every 60 min. Flash glucose monitors assessed glycemic control over a 22 h period. No differences were observed between conditions for overall 22 h glycemic control as measured by AUC total , mean glucose and time in hyperglycemia. During the 3.5 h post-lunch period, mean glucose was significantly lower during SRA6 (10.1 mmol·L -1 , 95%CI 9.2, 11.0) compared to SIT (11.1 mmol·L -1 , 95%CI 10.2, 12.0; P = 0.006). Post-lunch iAUC net was significantly lower during SRA6 (6.2 mmol·h·L -1 , 95%CI 3.3, 9.1) compared to SIT (9.9 mmol·h·L -1 , 95%CI 7.0, 12.9; P = 0.003). During the post-lunch period, compared to SIT (2.2 h, 95%CI 1.7, 2.6), time in hyperglycemia was significantly lower during SRA6 (1.5 h, 95%CI 1.0, 1.9, P = 0.001). Nocturnal mean glucose was significantly lower following the SRA3 condition (7.6 mmol·L -1 , 95%CI 7.1, 8.1) compared to SIT (8.1 mmol·L -1 , 95%CI 7.6, 8.7, P = 0.024)., Conclusions: With standardized total activity time, less-frequent active interruptions to sitting may acutely improve glycemic control; while more-frequent interruptions may be beneficial for nocturnal glucose in those with medication-controlled T2D., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Aims: To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education., Methods: Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00-10:00hrs; lunch 11:00-15:00hrs; dinner 17:00-21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9-10.0 mmol/L was the primary outcome., Results: MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00-24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis)., Conclusion: After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of Interest JCL reports no potential conflicts of interest relevant to this article. SV reports no potential conflicts of interest relevant to this article. SAM reports speaker honoraria from Roche and that her institution has received research support from Medtronic. BP reports speaker honoraria fees from Medtronic. MBA reports no potential conflicts of interest relevant to this article. MIdB reports no potential conflicts of interest relevant to this article. LAB reports grant funding from AstraZeneca. MGB reports no potential conflicts of interest relevant to this article. NDC reports personal fees from Medtronic and Abbott, grant funds from Ypsomed. PGC reports no potential conflicts of interest relevant to this article. EAD reports no potential conflicts of interest relevant to this article. DJHW reports no potential conflicts of interest relevant to this article. JK reports speaker fees from Novo Nordisk and AstraZeneca, advisory board fees from Abbott Diabetes. RJM reports research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, JDRF, Grey Innovations, The Diabetes Australia Research Trust/Program, and The National Health and Medical Research Council of Australia; honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Merck Sharp & Dohme, Norvartis, and Boehringer Ingelheim; travel support from Novo Nordisk, Sanofi, and Boehringer Ingelheim; is on the advisory boards for Novo Nordisk, Sanofi Aventis, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, and Astra Zeneca, and has been a principal investigator for industry sponsored clinical trials run by Novo Nordisk, Bayer, Johnson-Cilag, and Abbive. ACK reports no potential conflicts of interest relevant to this article. KK reports no potential conflicts of interest relevant to this article. RJM reports no potential conflicts of interest relevant to this article. WMC reports no potential conflicts of interest relevant to this article. CMS reports no potential conflicts of interest relevant to this article. KR reports no potential conflicts of interest relevant to this article. VJS reports no potential conflicts of interest relevant to this article. ST reports non-financial support from Abbott Diabetes. GMW reports no potential conflicts of interest relevant to this article. AJJ has received research support from Medtronic, the National Health and Medical Research Council, JDRF Australia and International, Sanofi-Aventis, Abbott, and Mylan and has served on advisory boards for Medtronic, Sanofi, and Abbott (Diabetes). TWJ reports no potential conflicts of interest relevant to this article. DNO has served on advisory boards for Abbott, Medtronic, MSD, Novo, Roche, and Sanofi; received research support from Medtronic, Novo, Roche, Lilly, and Sanofi; and travel support from Novo and MSD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin, and triglycerides in adults with medication-controlled type 2 diabetes (T2D)., Research Design and Methods: Participants ( n = 23, 10 of whom were female, with mean ± SD age 62 ± 8 years and BMI 32.7 ± 3.5 kg · m -2 ) completed a three-armed randomized crossover trial (6- to 14-day washout): sitting uninterrupted for 7 h (SIT), sitting with 3-min SRAs (half squats, calf raises, gluteal contractions, and knee raises) every 30 min (SRA3), and sitting with 6-min SRAs every 60 min (SRA6). Net incremental areas under the curve (iAUC net ) for glucose, insulin, and triglycerides were compared between conditions., Results: Glucose and insulin 7-h iAUC net were attenuated significantly during SRA6 (glucose 17.0 mmol · h · L -1 , 95% CI 12.5, 21.4; insulin 1,229 pmol · h · L -1 , 95% CI 982, 1,538) in comparison with SIT (glucose 21.4 mmol · h · L -1 , 95% CI 16.9, 25.8; insulin 1,411 pmol · h · L -1 , 95% CI 1,128, 1,767; P < 0.05) and in comparison with SRA3 (for glucose only) (22.1 mmol · h · L -1 , 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUC net were observed in comparison of SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUC net ., Conclusions: In adults with medication-controlled T2D, interrupting prolonged sitting with 6-min SRAs every 60 min reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance., (© 2021 by the American Diabetes Association.)

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs ( n  = 61) versus pump ( n  = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA 1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump ( P  = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively ( P  = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P  < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: 1 ) uninterrupted sitting (SIT), 2 ) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3 ) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D. NEW & NOTEWORTHY This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.

Objective: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes)., Research Design and Methods: Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks., Results: Participants were randomized to HCL ( n = 61) or control ( n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA 1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; P < 0.0001). For HCL, HbA 1c was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively., Conclusions: In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA 1c , and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous., (© 2020 by the American Diabetes Association.)

Background: The effects of empagliflozin on cardiac structure and function are not known., Aims: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with type 2 (T2D) diabetes using cardiac magnetic resonance (CMR) imaging., Methods: Twenty patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patients with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent CMR scans at baseline and 6 months. Inclusion criteria were established T2D, age < 75 years, estimated glomerular filtration rate ≥45 mL/min/1.73 m 2 ., Results: 17 of 20 in the empagliflozin group, and all of 8 in the control group completed the study. Empagliflozin therapy was associated with reduction in left ventricular end diastolic volume 155 mL (137 mL, 174 mL) at baseline to 145 mL (125 mL, 165 mL) at 6 months, P < 0.01, compared with the control group 153 mL (128 mL, 179 mL) at baseline and 158 mL (128 mL, 190 mL), not significant. There were no differences in measures of left ventricular mass, ejection fraction, heart rate or markers of cardiac fibrosis at baseline and 6 months in either group., Conclusions: This is the first CMR study to examine the effects of empagliflozin on cardiac function and structure, showing evidence of reduced end diastolic volume. This is likely to reflect change in plasma volume, and may explain the reduced cardiovascular death and heart failure seen in the EMPA-REG OUTCOME trial., (© 2019 Royal Australasian College of Physicians.)

Background: Reducing hyperglycemia while avoiding hypoglycemia is the key clinical goal in managing people with type 1 diabetes. Insulin delivery techniques and regimens are constantly evolving to achieve these goals. At present, use of multiple daily injections (MDI) is the standard of care, but there is increasing interest in continuous subcutaneous insulin infusion (CSII). There is a deficit of studies comparing long-term glycemic control and hypoglycemia outcomes between these therapeutic options. Methods: This was a single-center, retrospective cohort study of adults with type 1 diabetes. Data were derived from electronic medical records and included demographic and clinical factors. Participants had all undergone intensive diabetes education, followed by CSII or continued MDI. The primary outcome was difference in hypoglycemia, defined as the percentage of self-monitoring blood glucose levels less than 3.9 mmol/L. Up to 10 years of follow-up data were available, between 2000 and 2016. Results: There were 69 participants using CSII and 78 using MDI. Self-monitoring blood glucose data showed significantly less hypoglycemia with CSII by over 30%, occurring as early as the first year and sustained throughout the follow-up period ( P  < 0.001). This benefit of CSII on reducing hypoglycemia was independent of more frequent hypoglycemia and higher body weight at baseline, factors that were also independently associated with reduced hypoglycemia. Conclusions: In selected adults with type 1 diabetes, long-term CSII can provide long-term clinically relevant and sustained reductions in hypoglycemia, particularly in those with greater initial risk of hypoglycemia and higher body weight, and improved glycemic control compared with MDI.

Background & Aims: Chronic overconsumption of sugar-sweetened beverages (SSBs) is associated with unfavourable health effects, including promotion of obesity. However, the acute effects of consuming SSBs on glucose and lipid metabolism remain to be characterized in a real-world, post-prandial context of prolonged sitting. We quantified the acute effects of between-meal SSB consumption compared with water, on glucose and lipid metabolism in habitual soft drink consumers during prolonged sitting., Methods: Twenty-eight overweight or obese young adults [15 males; 23 ± 3 (mean ± SD) years, body mass index (BMI) 31.0 ± 3.6 kg/m 2 ) participated. During uninterrupted sitting and following standardized breakfast and lunch meals, each participant completed two 7-h conditions on separate days in a randomized, crossover design study. For each condition, participants consumed either a sucrose SSB or water mid-morning and mid-afternoon. Peak responses and total area under the curve (tAUC) over 7 h for blood glucose, insulin, C-peptide, triglyceride and non-esterified fatty acid (NEFA) concentrations were quantified and compared., Results: Compared to water, SSB consumption significantly increased the peak responses for blood glucose (20 ± 4% (mean ± SEM)), insulin (43 ± 15%) and C-peptide (21 ± 6%) concentrations. The tAUC for all these parameters was also increased by SSB consumption. The tAUC for triglycerides was 15 ± 5% lower after SSBs and this was driven by males (P < 0.05), as females showed no difference between conditions. The tAUC for NEFAs was 13 ± 5% lower after the SSB condition (P < 0.05)., Conclusions: Between-meal SSB consumption significantly elevated plasma glucose responses, associated with a sustained elevation in plasma insulin throughout a day of prolonged sitting. The SSB-induced reduction in circulating triglycerides and NEFAs indicates significant modulation of lipid metabolism, particularly in males. These metabolic effects may contribute to the development of metabolic disease when SSB consumption is habitual and co-occurring with prolonged sitting. Clinical Trial Registry number: ACTRN12616000840482, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000840482., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Use of continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes has become increasingly popular in recent years, with recent studies examining the efficacy of CSII use in pregnancy and in type 2 diabetes. However, there is very limited information on the benefit of CSII in older patients with type 1 diabetes. Electronic medical records were retrospectively analyzed for patients with type 1 diabetes undertaking structured patient education and initiated on CSII or multiple daily injections (MDI) between 2000 and 2016. Outcomes examined related to changes in glycemic parameters and weight and utilization of healthcare resources. Data relating to 293 patients fulfilled the inclusion criteria, with up to 10 years of follow-up data available. For patients commencing CSII, glycemic and weight outcomes and utilization of healthcare resources were similar in older compared with younger patients. For older patients, use of CSII was associated with better glycemic outcomes at the cost of a small increase in healthcare resources compared with MDI. CSII can be used effectively and safely in the longer term in carefully selected older patients with type 1 diabetes, with similar outcomes as observed in younger patients using CSII, and potentially better glycemic outcomes than MDI in older patients.

Aims/hypothesis: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m 2 ) and type 2 diabetes (HbA 1c 53-97 mmol/mol [7-11%] and fasting glucose <15.6 mmol/l)., Methods: Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated individuals vs placebo that became evident during late-stage development of the drug., Results: In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25; n = 19; p < 0.0001). The change in HbA 1c (baseline 67 mmol/mol [8.3%]) was -6.6 ± 2.2 mmol/mol (-0.6 ± 0.2%) with placebo vs -21.9 ± 2.2 mmol/mol (-2.0 ± 0.2%) or -21.9 ± 3.3 mmol/mol (-2.0 ± 0.3%) with 1.2 or 1.8 mg beloranib (p < 0.0001), respectively. The most common beloranib adverse events were sleep related. One beloranib-treated participant experienced a non-fatal pulmonary embolism., Conclusions/interpretation: MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA 1c ., Trial Registration: ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc.

Introduction: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes., Methods and Analysis: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA 1c , severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users., Ethics and Dissemination: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications., Trial Registration Number: ACTRN12617000520336; Pre-results., Competing Interests: Competing interests: MIdB and NDC report receiving speaker honoraria from Medtronic. DJHW reports receiving speaker and advisory board honoraria from Medtronic. RWM reports receiving conference travel and accommodation support from Medtronic. JS reports that the ACBRD has received honoraria from Medtronic in relation to her speaking engagements and role in advisory boards. DNON reports receiving speaker honoraria and research grants from Medtronic., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10 pmol/l instead of 48 ± 10 pmol/l. This mistake also impacts on data reported in Table 4.

Aims/hypothesis: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans., Methods: We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [ 18 F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention., Results: Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (-57 ± 6% vs -12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (-50 ± 10% vs -6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected., Conclusions/interpretation: The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs., Trial Registration: ClinicalTrials.gov NCT02236962 FUNDING: This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.

Aims/hypothesis: We aimed to examine the effect of interrupting 7 h prolonged sitting with brief bouts of walking or resistance activities on 22 h glucose homeostasis (including nocturnal-to-following morning hyperglycaemia) in adults with type 2 diabetes., Methods: This study is an extension of a previously published randomised crossover trial, which included 24 inactive overweight/obese adults with type 2 diabetes (14 men; 62 ± 6 years) who completed three 7 h laboratory conditions, separated by 6-14 day washout periods: SIT: (1) prolonged sitting (control); (2) light-intensity walking (LW): sitting plus 3 min bouts of light-intensity walking at 3.2 km/h every 30 min; (3) simple resistance activities (SRA): sitting plus 3 min bouts of simple resistance activities (alternating half-squats, calf raises, brief gluteal contractions and knee raises) every 30 min. In the present study, continuous glucose monitoring was performed for 22 h, encompassing the 7 h laboratory trial, the evening free-living period after leaving the laboratory and sleeping periods. Meals and meal times were standardised across conditions for all participants., Results: Compared with SIT, both LW and SRA reduced 22 h glucose [SIT: 11.6 ± 0.3 mmol/l, LW: 8.9 ± 0.3 mmol/l, SRA: 8.7 ± 0.3 mmol/l; p < 0.001] and nocturnal mean glucose concentrations [SIT: 10.6 ± 0.4 mmol/l, LW: 8.1 ± 0.4 mmol/l, SRA: 8.3 ± 0.4 mmol/l; p < 0.001]. Furthermore, mean glucose concentrations were sustained nocturnally at a lower level until the morning following the intervention for both LW and SRA (waking glucose both -2.7 ± 0.4 mmol/l compared with SIT; p < 0.001)., Conclusions/interpretation: Interrupting 7 h prolonged sitting time with either LW or SRA reduced 22 h hyperglycaemia. The glycaemic improvements persisted after these laboratory conditions and nocturnally, until waking the following morning. These findings may have implications for adults with relatively well-controlled type 2 diabetes who engage in prolonged periods of sitting, for example, highly desk-bound workers., Trial Registration: anzctr.org.au ACTRN12613000576729 FUNDING: : This research was supported by a National Health and Medical Research Council (NHMRC) project grant (no. 1081734) and the Victorian Government Operational Infrastructure Support scheme.

Objective: Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D)., Methods: In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter., Results: Compared with SIT, mean resting SBP and DBP were significantly reduced (P < 0.001) for both light-intensity walking (mean ± SEM; -14 ± 1/-8 ± 1 mmHg) and SRA (-16 ± 1/-10 ± 1 mmHg), with a more pronounced effect for SRA (P < 0.05 versus light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (-0.3 ± 0.1 nmol/l) and SRA (-0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P < 0.05). Mean resting heart rate was lowered by light-intensity walking (-3 ± 1 bpm; P < 0.05), but not SRA (-1 ± 1 bpm)., Conclusion: Interrupting prolonged sitting with brief bouts of light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.

Objective: To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D)., Research Design and Methods: In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6-14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h(-1)) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions., Results: Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L(-1) [95% CI 20.4-28.0] vs. LW 14.8 [11.0-18.6] and SRA 14.7 [10.9-18.5]), insulin (SIT 3,293 pmol · h · L(-1) [2,887-3,700] vs. LW 2,104 [1,696-2,511] and SRA 2,066 [1,660-2,473]), and C-peptide (SIT 15,641 pmol · h · L(-1) [14,353-16,929] vs. LW 11,504 [10,209-12,799] and SRA 11,012 [9,723-12,301]) (all P < 0.001). The iAUC for triglycerides was significantly attenuated for SRA (P < 0.001) but not for LW (SIT 4.8 mmol · h · L(-1) [3.6-6.0] vs. LW 4.0 [2.8-5.1] and SRA 2.9 [1.7-4.1])., Conclusions: Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

• Type 2 diabetes mellitus (T2DM) is progressive; the more intensively it is treated, the greater is the risk of hypoglycaemia and weight gain. Achieving treatment intensification while mitigating these risks presents a challenge to patient management. • Basal insulins provide control of fasting glucose; however, their utility in the control of postprandial glucose excursions is limited. • Glucagon-like peptide-1 (GLP-1) receptor agonists stimulate glucose-medicated insulin secretion, suppress glucagon secretion, delay gastric emptying and decrease appetite. Use of GLP-1 receptor agonists in combination therapy with basal insulin offers an alternative approach to intensification of insulin therapy. • Prospective interventional trials demonstrate that GLP-1 receptor agonists added to basal insulin decrease postprandial glucose levels, lower HbA1c levels, decrease weight and lower basal insulin requirements without increasing the risk of major hypoglycaemic events. • The current clinical data are limited by the lack of any data on the long-term effects of GLP-1 receptor agonists over additional prandial regimens; they may be beneficial or deleterious. • Although cost, gastrointestinal side effects and long-term safety should be taken into account when considering this combination, it appears to be growing in popularity and is likely to be an important therapeutic option for T2DM in the future.

Background: Continuous subcutaneous insulin infusion (CSII) and intensive multiple daily insulin injections (iMDI) program are treatment options in patients with type 1 diabetes not achieving optimal glycemic control. The long-term effects of CSII in patients with type 1 diabetes in comparison with those educated for iMDI are poorly documented., Research Design and Methods: Medical records for patients commenced on CSII or undertaking an iMDI program between 2000 and 2011 were extracted. Change in hemoglobin A1c (HbA1c), hypoglycemia, and weight were analyzed. Prior to CSII or iMDI commencement, all patients were on basal bolus analog insulin. Data from blood glucose meter downloads before and 6 months after CSII and iMDI were also analyzed., Results: One hundred twenty-six CSII and 121 iMDI patients were studied, with mean (±SD) follow-up of 39±26 and 48±26 months, respectively. For CSII, HbA1c was significantly lower than baseline at every time period up to 36 months. Peak HbA1c reduction was 0.64% at 6 months, following which the HbA1c change declined. For iMDI, HbA1c was significantly reduced only at 6 months, by 0.15%. Glucose meter data were available for 119 patients. CSII-treated patients had a significant decrease in mean glucose and glucose SD with no change hypoglycemia at 6 months compared with baseline; no differences were observed for iMDI-treated patients., Conclusions: CSII in type 1 diabetes is associated with improved glycemic control with no increase in hypoglycemia. HbA1c improvement declined over time, suggesting a need for re-education after CSII commencement. The iMDI program did not have significant glycemic benefits.