Peter Gerard Fegan

Incretin mimetics as obesity therapy induce substantial weight and fat loss but also decrease lean soft tissue mass, possibly impairing skeletal muscle function. Here, in this two-arm randomized controlled trial of adding resistance exercise (REx) to tirzepatide (T), 120 adults with overweight or obesity were treated with tirzepatide and randomized to thrice-weekly resistance exercise training or usual activities for 40 weeks. Tirzepatide was safe, and most participants tolerated up-titration to 15 mg weekly. Adherence to resistance exercise was 91%. Weight loss achieved was similar (T = −22.61 kg, T+REx = −22.28 kg, P = 0.694). For primary outcomes, loss of total fat mass was similar (T = −17.19 kg, T+REx = −17.98 kg, P = 0.700; between-group difference = −0.77 kg, 95% confidence interval (CI): −2.14 kg to 0.60 kg), but resistance exercise reduced loss of total lean soft tissue mass (T = −4.67 kg, T+REx = −3.57 kg, P < 0.001; between-group difference = 1.09 kg, 95% CI: 0.43−1.75 kg). For related endpoints, resistance exercise reduced loss of appendicular lean soft tissue mass (T = −3.55 kg, T+REx = −2.92 kg, P < 0.001). Upper and lower body muscle strength decreased with tirzepatide (bench press −4.09 kg, lat pulldown −4.42 kg, knee extension −4.42 kg) but increased with T+REx (+4.68 kg, +8.58 kg, +5.88 kg, respectively, all P < 0.001 versus tirzepatide). In conclusion, resistance exercise training attenuated loss of total lean soft tissue mass, representing an effective adjunct to tirzepatide anti-obesity therapy. Australian New Zealand Clinical Trials Registry identifier: ACTRN12623001236684.

This study presents real‐world data on low‐density lipoprotein cholesterol (LDL‐C) management in the first 200 patients seen at a new multidisciplinary cardiometabolic clinic from January 2023, with follow‐up until April 2024. The cohort had a mean ± standard deviation age of 52 ± 14 years, 51% were male, 69 (35%) had familial hypercholesterolaemia and 66 (33%) had cardiovascular disease. Lipid‐lowering therapies were escalated in 120 (60%) patients. Median low‐density lipoprotein cholesterol level decreased with initiation of evolocumab (69%), inclisiran (56%), statin (45%) and ezetimibe (21%). In patients with a history of statin intolerance, 19 (43%) re‐initiated or increased statin dose.

Introduction: Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular disease (CVD), yet many patients do not attain recommended lipid targets. Aims: We aimed to identify patient and clinician factors affecting lipid management. Methods: Anonymous online surveys were developed to assess perspectives from adults with T1D and prescribing doctors. Participants were recruited from three Australian centres. Patients were asked about their understanding of CVD risk, cholesterol and cholesterol‐lowering medications. Doctors were surveyed on CVD risk assessment and lipid management. Results: Among 547 patients, ~1 in 2 reported their doctor had not discussed CVD risk, they preferred lifestyle changes over medications and viewed glucose as more important than cholesterol for CVD risk reduction. Whilst ~1 in 2 statin‐naïve patients would take statins if recommended, ~1 in 6 expressed concerns about side effects. All 41 clinicians believed that CVD risk should be routinely assessed; however, ~1 in 3 often had inadequate time to discuss dyslipidaemia and prioritised glycaemia before considering statins. Doctors identified adherence, concerns about side effects, negative beliefs/attitudes about statins and future pregnancy as barriers to lipid management. Conclusion: The identified patient‐ and clinician‐related factors should be addressed in future studies and in clinics to optimise lipid management in T1D.

Cardiovascular disease (CVD) is a significant burden in individuals with type 1 diabetes mellitus (T1DM). Yet the optimal method of CVD risk stratification remains uncertain. We found that the new Australian CVD risk calculator could overestimate risk category compared with the Steno Type 1 Risk Engine and underestimate risk category compared with the new Swedish/Scottish prediction tool, both of which were validated for T1DM. More research is needed to derive a CVD risk assessment pathway for individuals with T1DM in Australia.

Aims/hypothesis: Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU. Methods: Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D−/I−), not deep but infected (D−/I+), deep with no infection (D+/I−) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression. Results: Of 513 patients, 241 (47.0%) were in the D−/I− group, 110 (21.4%) were in the D−/I+ group, 35 (6.8%) were in the D+/I− group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220–551) and 404 days (IQR 228–576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; pp=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D−/I− 7.9%; D−/I+ 15.5%; D+/I− 14.3%; D+/I+ 26.8%; pp=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes. Conclusions/interpretation: Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation. Graphical

Background: Severe burns may induce hyperglycaemia in the absence of diabetes, but how glucose trajectories relate to burns outcomes is unclear. Aim: To assess incidence of hyperglycaemia following acute burn injury, and associations with diabetes history and length of stay (LOS). Methods: Retrospective cohort study of adults admitted with acute burns to tertiary centres. Blood glucose level (BGL), hyperglycaemic episodes (BGL ≥ 11.1 mmol/L) and hyperglycaemic days were recorded. Stress hyperglycaemia was defined as BGL ≥ 11.1 mmol/L without a diabetes history. Results: A total of 30 participants had a diabetes history and 260 did not. Participants with known diabetes had higher mean BGLs (9.7 vs. 9.0 mmol/L, p < 0.001), more hyperglycaemic episodes (28.0 vs. 17.2%, p < 0.001) and hyperglycaemic days (51 vs. 21%, p < 0.001), compared to those without diabetes, despite smaller burns (total body surface area 1.0 vs. 14.8%, p < 0.001). Fourteen participants with stress hyperglycaemia had similar BGLs (at admission 10.3 vs. 11.5 mmol/L; during inpatient stay 9.9 vs. 9.8 mmol/L), more severe burns (15.6% vs. 1.0% TBSA) and longer LOS (18 vs. 7 days, p < 0.001) compared to participants with known diabetes. Extent of burns, having NGT nutrition, age, having inpatient BGL monitoring in the setting of diabetes, or having inpatient BGL monitoring in the absence of diabetes were associated with longer LOS. Conclusions: In participants with known diabetes, small burn injuries were associated with hyperglycaemia. Stress hyperglycaemia can be triggered by major burn injuries, with early and sustained elevation of BGLs. Further research is warranted to improve inpatient management of BGL in patients with acute burn injury.