Introduction. Class 3 obesity (BMI≥40 kg/m2) is a growing health problem worldwide associated with considerable comorbidity including Type 2 diabetes mellitus (T2DM). The multidisciplinary medical management of obesity can be difficult in T2DM due to potential weight gain from medications including sulphonylureas and insulin. However, newer weight-neutral/losing diabetes medications can aid additional weight loss. The aim of this study was to compare weight loss outcomes of patients with and without T2DM, and in patients with T2DM, to compare diabetes outcomes and change in medications at 6 months. Methods. All patients entering a multidisciplinary weight management metabolic program in a publicly funded hospital clinic in Sydney between March 2018 and March 2019, with BMI≥40 kg/m2 and aged ≥18 years were included. Data was collected from patient clinical and electronic notes at baseline and 6 months. Results. Of the 180 patients who entered the program, 53.3% had T2DM at baseline. There was no difference in percentage weight loss in those with or without T2DM (4.2±4.9% vs. 3.6±4.7%, p=0.35). Additionally, T2DM patients benefited from a 0.47% reduction in HbA1c (p<0.01) and a reduction in the number of medications from baseline to 6 months (1.8±1.0/patient vs. 1.0±1.2/patient, p<0.001). T2DM patients who started on weigh-neutral/losing medications in the program lost more weight than those started on weight-gaining medications (7.7±5.3% vs. 2.4±3.8%, p=0.015). Conclusions. Patients with class 3 obesity had significant weight loss at 6 months in this program. Patients with T2DM at baseline had comparable weight loss at 6 months, a significant improvement in glycaemic control, and a reduction in diabetes medication load. Additionally, patients with T2DM who were started on weight-neutral/losing medications lost significantly more weight than those started on weight-gaining medications, and these medications should be preferentially used in class 3 obesity and comorbid T2DM.
We aimed to assess weight loss and metabolic outcomes by severity of weight-related complications following an intensive non-surgical weight management program (WMP) in an Australian public hospital. A retrospective cohort study of all patients aged ≥18 years with body mass index (BMI) ≥ 40 enrolled in the WMP during March 2018–March 2019 with 12-month follow-up information were stratified using the Edmonton Obesity Staging System (EOSS). Of 178 patients enrolled in the WMP, 112 (62.9%) completed at least 12 months’ treatment. Most patients (96.6%) met EOSS-2 (56.7%) or EOSS-3 (39.9%) criteria for analysis. Both groups lost significant weight from baseline to 12 months; EOSS-2: 139.4 ± 31.8 kg vs. 131.8 ± 31.8 kg (p < 0.001) and EOSS-3: 141.4 ± 24.2 kg vs. 129.8 ± 24.3 kg (p < 0.001). After adjusting for baseline age, sex and employment status, mean weight loss was similar but a greater proportion of EOSS-3 achieved >10% weight loss compared to EOSS-2, (40% vs. 15.9%, p = 0.024). Changes in metabolic parameters including HbA1c, BP and lipids did not differ between EOSS-2 and 3. Despite increased clinical severity, adult patients with class 3 obesity achieved clinically meaningful weight loss and similar improvements in metabolic parameters compared to patients with less severe complications after 12 months in an intensive non-surgical WMP.
Beige and brown fat consume glucose and lipids to produce heat, using uncoupling protein 1 (UCP1). It is thought that full activation of brown adipose tissue (BAT) may increase total daily energy expenditure by 20%. Humans normally have more beige and potentially beige-able fat than brown fat. Strategies to increase beige fat differentiation and activation may be useful for the treatment of obesity and diabetes. Mice were fed chow or high-fat diet (HFD) with or without the iron chelator deferasirox. Animals fed HFD + deferasirox were markedly lighter than their HFD controls with increased energy expenditure (12% increase over 24 h, p < 0.001). Inguinal fat from HFD + deferasirox mice showed increased beige fat quantity with greater Ucp1 and Prdm16 expression. Inguinal adipose tissue explants were studied in a Seahorse bioanalyser and energy expenditure was significantly increased. Deferasirox was also effective in established obesity and in ob/ob mice, indicating that intact leptin signalling is not needed for efficacy. These studies identify iron chelation as a strategy to preferentially activate beige fat. Whether activating brown/beige fat is effective in humans is unproven. However, depleting iron to low-normal levels is a potential therapeutic strategy to improve obesity and related metabolic disorders, and human studies may be warranted.
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