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25th May 2021
Cancer of the breast is the most common form of cancer in women although with an early diagnosis, the 5-year survival prognosis ranges from 86 to 99%. Nevertheless, women who survive breast cancer have a 17% increased risk for a second cancer compared to the general population. One factor known to be associated with cancer is obesity with one US study estimating that 40% of all cancer diagnoses occurred in people who were either overweight or obese. However, while much attention has been paid to the effect of obesity on the development of an initial cancer, far less is known about how obesity impacts on the development of a second cancer. As a result, a team from Kaiser Permanente, Denver, US, sought to examine the association between body mass index (BMI) and a second cancer among women who survived invasive breast cancer. Data were extracted from an electronic database and a surveillance tumour registry which provided information on the incidence and type of secondary cancers that occurred. Height and weight measurements within two years prior through one year after the date of the initial breast cancer diagnosis were used to calculate the BMI. All women included had surgery as part of their initial breast cancer and had no evidence of a second cancer one year later. The study outcomes included all second cancers, cancers for which there was a known association with obesity (e.g., oesophageal adenocarcinoma), and ER-positive second breast cancers.
A total of 6481 women were included in the analysis with a mean age of 60.2 years, of whom 33.4% were classed as overweight or obese (33.8%) at the time of their initial breast cancer diagnosis. During a median follow-up of 88 months, 822 (12.7%) women developed a second cancer, of which 508 (61.8%) were obesity-related and 333 (40.5%) were breast cancer, the majority of which (69.4%) were ER-positive. The authors calculated that every 5 unit increase in BMI was associated with a 7% increased risk of developing any second cancer (relative risk, RR = 1.07, 95% CL 1.01–1.14), a 13% increased for an obesity-related cancer and by 15% for a second ER-positive breast cancer.
The authors calculated that the risk of a second cancer was increased by 5% for every 5 unit increase in BMI. They concluded that these data had important public health implications given the prevalence of obesity and underscored the need for effective preventative strategies.
Feigelson HS et al. Body Mass Index and Risk of Second Cancer Among Women with Breast Cancer. J Natl Cancer Inst 2021
18th January 2021
The monoclonal antibody bimagrumab binds to and blocks the activity of the activin type II receptor (ActRII), promoting skeletal muscle hypertrophy and reducing body fat mass. Given this potential action, researchers from Pennington Biomedical Research Centre, Louisiana State University, in the US, hypothesised that the drug might represent a beneficial approach to the management of obese, type 2 diabetic patients. They recruited type 2 diabetes aged between 18 and 75 years with a glycated haemoglobin (HbA1C) of 6.5 to 10%, a body mass index (BMI) of 28 to 40 and a weight of between 65 and 140kg. All patients were prescribed either metformin (as mono-therapy), dipeptidyl peptidase 4 (DPP4) inhibitors, (again as mono-therapy) or a combination of both drugs, although a small number were not prescribed any diabetic medicines. These treatments were permitted because of their weight neutral effect. Eligible participants were randomised 1:1 to either Bimagrumab (10mg/kg to a maximum of 1200mg in 5% dextrose) or placebo (5% dextrose) via 30-minute intravenous infusion every 4 weeks for a total of 48 weeks and both clinicians and patients were blinded to allocation. The primary endpoint was a change from baseline to week 48 in total fat mass (FM) which was measured by dual energy X-ray absorptiometry. Secondary endpoints included change in diabetic status (HbA1C), body weight, BMI and both HOMA2 and the Matsuda index which are measures of insulin sensitivity.
A total of 75 patients were randomised to either bimagrumab (37) or placebo (38). The mean age of those assigned to bimagrumab was 60.7 years (62.2% female). At week 48, total FM decreased by a mean of 7.49 kg in the bimagrumab group vs 0.18 kg in the placebo group (p < 0.01). Similarly, there were significant reductions in BMI (2.19 vs 0.28, p < 0.001), body weight (5.90 kg vs 0.79 (p < 0.01) and HbA1C levels (0.76 vs 0.04, p < 0.05). Interestingly, the bimagrumab group also saw a significant increase in lean muscle mass compared to the placebo group (1.70 kg vs 0.4 kg, p < 0.001). However, there were no significant changes to either measure of insulin sensitivity or in use of anti-diabetic medication. Commenting on their findings, the authors noted that treatment with bimagrumab led to a small increase in lean muscle mass which is a beneficial effect given that muscle loss is typically observed when type 2 diabetes adopt a low-calorie diet.
They concluded that inhibition of ActRII may provide a novel pathway for the management of excess body fat and metabolic disturbances as seen in type 2 diabetics.
Heymsfield SB et al. Effect of Bimagrumab vs placebo on body fat mass among adults with type 2 diabetes and obesity. A phase 2 randomised clinical trial. JAMA Netw Open 2021
30th November 2020
The precise reasons why obesity enhances the risk of a more severe outcome in COVID-19 remains unclear. Nevertheless, obesity is associated with several other additional risk factors such as cardiometabolic, thromboembolic and pulmonary disease and it is likely that it is this combination of factors that raises the overall risk. For example, obese patients have higher levels of pro-inflammatory cytokines and oxidative stress which can impact on both the innate and adaptive immune system, all of which may contribute to a worse prognosis. Metabolic surgery in obese patients leads to improvements in cardiovascular risk factors and the amelioration of the pro-inflammatory state linked with obesity.
In a retrospective study of patients testing positive for COVID-19, researchers from the Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Ohio, US, set out to examine the relationship between prior metabolic surgery and the severity of COVID-19 in severely obese patients. A total of 33 individuals who had prior metabolic surgery (the surgical group) were identified and were matched 1:10 to non-surgical patients to create a cohort with a body mass index (BMI) greater than or equal to 40kg/m2 at the time of testing. The pre-specified endpoints examined were: admission to intensive care, need for mechanical ventilation, dialysis during their hospital stay and mortality.
Data on a total of 363 patients, including the 33 who had prior metabolic surgery were available for analysis. The surgical group had a mean age of 46.1 years (78% female) with a mean BMI of 37.2±7.1 compared to 46.7± 6.4kg/m2 in the control group. A subsequent univariate analysis showed that 18.2% of those in the surgery group and 42.1% in the control group were admitted to hospital because of their infection with COVID-19. A prior history of metabolic surgery was associated with a statistically lower odds of being admitted to hospital (odds ratio = 0.31, 95% CI 0.11 – 0.88, p = 0.028). Furthermore, none of the surgical group patients experienced one of the four pre-specified endpoints. In contrast, 13% of those in the control group were admitted to intensive care, 6.7% required mechanical ventilation, 1.5% dialysis and 2.4% died. The authors suggested that prior metabolic surgery was associated with a lower severity of COVID-19 infection but recognised that these observations were based on a small sample size and they were also unable to account for their findings.
They concluded by calling for more research to understand the mechanistic role of both obesity and intentional weight loss on COVID-19 infection.
Aminian A et al. Association of prior metabolic and bariatric surgery with severity of coronavirus disease 2019 (COVID-19) in patients with obesity. Surg Obes Relat Dis 2020. https://doi.org/10.1016/j.soard.2020.10.026