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Take a look at a selection of our recent media coverage:
9th May 2022
Adult asthmatics and, in particular individuals who have had the disease for a long period of time and use oral corticosteroids, have been found to have a small, but significantly increased risk of developing obesity compared with those without the disease. This was the main finding of a study by researchers from the Division of Pulmonary Medicine, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Canada.
Data for 2016 shows that more than 1.9 billion adults were overweight and, of these, over 650 million were obese. It has also been found that while obese people report more incident asthma, it is not clear whether this represents reactivation of previously diagnosed asthma or the onset of new cases. Nevertheless, data for children are much clearer with one study finding that among asthmatics, there is a 51% increased risk of developing obesity during childhood and adolescence compared to children without asthma.
Since the relationship between asthma and obesity in adults remains unclear, in the present study, the researchers sought to investigate the occurrence of obesity due to asthma among participants in the European Community Respiratory Health Survey (ECRHS) over 2 periods of 10 years, which were labelled ECRHS-II and ECRHS-III. ECRHS-I began in 1990 and recruited over 18,000 participants and had two follow-up periods at approximately 10-year intervals. The researchers excluded those with a diagnosis of obesity at baseline and then classified individuals as either having ‘no asthma’ or ‘current asthma’. Additional data on the duration of asthma, treatments used and the presence or absence of atopy (based on serum levels of IgE to common allergens) was also collected.
Adult asthmatics and the risk of obesity
The research team included 7576 participants with a baseline mean age of 34 years (51.5% female) in ECRHS I-II and 4976 participants (mean age 42, 51.3% female) in ECRHS-II-III.
The risk of developing obesity was higher among asthmatics compared to those without the condition (relative risk, RR = 1.22, 95% CI 1.07 – 1.38). Furthermore, this risk was also higher among those without atopy (RR = 1.47), for individuals who had asthma for longer than 20 years (RR = 1.32, 95% CI 1.10 – 1.59) and for those using oral corticosteroids (RR = 1.99, 95% CI 1.26 – 3.15). In subgroup analysis, smokers also had a higher risk of becoming obese compared to non-smokers (RR = 1.46).
The authors concluded that adult asthmatics were at a greater risk of developing obesity in later life, especially those with longstanding disease, who were using oral corticosteroids and had non-atopic asthma.
Moitra S et al. Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS Thorax 2022
In a press release from the manufacturer, Lilly, headline results from a trial have shown that use of the anti-diabetic agent tirzepatide 15 mg for 72 weeks in a Phase III randomised trial, led to a 22.5% reduction in weight among those classed as either overweight and obese patients.
Tirzepatide is described as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is in development for the treatment of type 2 diabetes. Early data from studies in mice suggested that chronic administration of the drug, could reduce both food intake and body weight and how it was suitable for administration on a weekly basis. Moreover, studies in humans have shown the drug to be an effective treatment for patients with type 2 diabetes. For example, in randomised, double-blind phase 3 trial in patients with type 2 diabetes, tirzepatide was found to produce significantly better efficacy with regard to glucose control and weight loss than the comparator, dulaglutide. In addition, in an open-label, 40-week trial, in 1879 patients with type 2 diabetes, tirzepatide was found to be non-inferior and superior to semaglutide with respect to the mean change in the glycated haemoglobin level from baseline to 40 weeks.
Tirzepatide and weight loss
Although the evidence points to tirzepatide being an effective treatment for type 2 diabetes, for the current press release, the manufacturer focused on the results from the SURMOUNT-1 trial in which the drug was administered to overweight or obese patients without type 2 diabetes, with a mean baseline body weight of 105 kg.
The SURMOUNT-1 trial randomised 2,539 participants in a 1:1:1:1 ratio to different doses of tirzepatide (5mg, 10mg or 15mg) or placebo and the treatment was given as an adjunct to a reduced-calorie diet combined with increased physical activity. All of the participants receiving tirzepatide were started at a dose of tirzepatide 2.5mg once-weekly and then increased in a step-wise approach at four-week intervals to their final randomised maintenance doses. The co-primary endpoints of the study were to show that tirzepatide 10mg and/or 15 mg were superior to placebo in the percentage reduction in body weight compared with baseline and the percentage of participants who achieved a ≥5% body weight reduction at 72 weeks, again compared with placebo.
At the end of the trial, among those taking tirzepatide, average weight reductions were 16.0% (5mg), 21.4% (10mg) and 22.5% (15mg), compared with 2.4% in the placebo arm. Furthermore, the proportion of participants achieving a body weight reduction of ≥5% were 85% (5mg), 89% (10mg), 91% (15mg), and 35% (placebo).
The press release also demonstrates how tirzepatide was well tolerated with the most commonly reported adverse events being gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose escalation period. Adverse effects included nausea, diarrhoea, vomiting and constipation which were more frequently experienced compared to placebo. In fact, the overall treatment discontinuation rates due to adverse events were 14.3% (5mg), 16.4% (10mg), 15.1% (15mg) and 26.4% (placebo).
The company is also currently undertaking further trials in overweight patients with type 2 diabetes.
10th February 2022
Sleep extension by as little as one hour per night leads a reduction in energy intake and could form part of a weight loss or obesity prevention programme. This is according to a study by researchers from the Department of Medicine, The University of Chicago, US.
Obesity is a major public health concern, with one US study finding that in 2017–2018, the age adjusted prevalence of obesity in adults was 42.4%, and that there were no significant differences between the sexes. The increase in levels of obesity have been driven over the past three decades by a substantial increase in total energy intake and some evidence suggests that short sleep duration significantly increased the risk of obesity. The authors of this analysis added that compared to a 7 hour sleep duration per day, the risk of obesity increases by 9% for each hour decrease in sleep duration. Additionally, another review concluded that short sleep duration appears independently associated with weight gain and sleep restriction results in a significant increase in subjective hunger and in particular, restricting sleep to a duration of ≤5.5 hours/day increases daily energy intake.
However, many of the above studies were undertaken in dedicated sleep laboratories and it is therefore unclear to what extent the findings are generalisable to a real-life setting. For the present study, the US team sought to determine whether a sleep extension intervention in overweight, adults aged 21 to 40 years of age, who habitually achieved less than 6.5 hours sleep per night, could positively impact on energy balance and body weight. These individuals were initially screened for two weeks to determine their sleeping habits and then randomised to either a two-week sleep extension group, which involved an individualised sleep hygiene counselling session, designed to extent their sleep time to 8.5 hours/night, or two-week continued habitual sleep (the control group).
Individuals sleep-wake patterns were continuously monitored at home using a wrist actigraph over a 4-week period. Total energy expenditure was measured with doubly labelled water and every two weeks the change in energy stores was estimated from daily measurements of home weights and changes in body composition. The primary outcome was the change in energy intake from baseline.
Sleep extension and changes in energy intake
A total of 80 individuals with a mean age of 29.8 years (51.3% male) were randomised to the sleep extension or control groups. Among those assigned to the sleep extension arm, energy expenditure decreased significantly compared to the control group (-270.4 kcal/day, 95% CI -393.4 to -147.4, p < 0.001). Furthermore, there was a significantly different increase of energy intake from baseline in the control group (114.9 kcal/day).
Among those in the sleep extension group, the duration of sleep increased by approximately 1.2 hours/night (95% CI 1 to 1.4 hours, p < 0.01). When comparing both groups, for each 1-hour increase in sleep duration, there was an associated decrease in energy intake of approximately 162 kcal/day. Interestingly, the sleep extension group experienced a mean decrease in weight of -0.87 kg (95% CI -1.29 to -0.35, p = 0.001) compared to a weight increase in the controlled group of 0.39 kg.
The authors concluded that sleep extension reduced energy intake and suggested that improving and maintaining healthy sleep duration in the longer term could form part of an obesity prevention or weight loss program.
Tasali E et al. Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial JAMA Intern Med 2020
3rd November 2021
A sustained weight loss over several years, not only delays but reduces the overall incidence of adverse cardiometabolic outcomes including type 2 diabetes, hypertension and hyperlipidaemia. This was the conclusion of a retrospective analysis of nearly 50,0000 patients by researchers from Geisinger Health, Pennsylvania, US. According to the world Health Organisation (WHO), worldwide levels of obesity have tripled since 1975 and in 2016, more than 1.9 billion adults, 18 years and older, were overweight and of these over 650 million were obese. However, obesity is not limited to adults and WHO data also suggests that in 2020, 39 million children under the age of 5 were overweight or obese. In a 2017 article, the World Obesity Federation issued a position statement, arguing that obesity should be perceived as a chronic relapsing disease process in which an abundance of food, coupled with low levels of physical activity, various environmental factors and genetic susceptibilities, all interact to create a positive energy balance. Increased weight and obesity are linked to a higher incidence of cardiovascular diseases, musculoskeletal disorders and some cancers. Nevertheless, even a 5% sustained weight loss improves metabolic function in multiple organs although longer term maintenance of weight loss is challenging, with one meta-analysis of 29 weight loss studies concluding that “weight-loss maintenance 4 or 5 y after a structured weight-loss program averages 3.0 kg or 23% of initial weight loss.”
However, what remains unclear is the impact of sustained weight loss on the development of cardiometabolic diseases and for the present study, researchers turned to in data held the Geisinger Health System, which represents one of the largest healthcare organisations in the US. The team looked at adult patients for whom there were 3 or more electronic health record entries for weight measurements within a 2-year period. Individuals were then categorised as obesity maintainers (OM), i.e., those with a history of obesity and who maintained their weight within 3% of their baseline levels; weight loss rebounders (WLRs) who had lost > 5% body weight but had regained > 20% of their 1-year loss and finally weight loss maintainers (WLMs), who again loss > 5% of their body weight but maintained > 80% of their 1-year weight loss. The outcomes of interest were the development of type 2 diabetes, hypertension and hyperlipidaemia, all of which were extracted from the electronic health records. In their analysis, researchers adjusted for several factors such as age, gender and various co-morbidities.
The sample contained 49,327 individuals with a mean age of 50.4 years (60.2% female) with the majority classed as OM (the reference group) and the whole sample were followed-up for a mean period of 6.6 years. After 5 years, 11.1% of the OM, 9.1% of the WLR and 6.5% of the WLM had developed type 2 diabetes and those in the sustained weight loss group (WLM) had a 33% lower risk of developing incident type 2 diabetes (adjusted hazard ratio, aHR = 0.68, 95% CI 0.62 – 0.74, p < 0.0001). Similarly, the WLM had a reduced risk of developing hypertension (aHR = 0.72) and hyperlipidaemia (aHR = 0.86).
Based on these findings, the authors concluded that sustained weight loss was associated with a delayed onset of cardiometabolic diseases and that these associations are enhanced in those with the greatest weight loss.
Bailey-Davis L et al. Impact of Sustained Weight Loss on Cardiometabolic Outcomes. Am J Cardiol 2021
14th September 2021
Type 2 diabetes is characterised by a progressive loss of beta-cell function in the pancreas and recent data have shown that intermittent very-low calorie diets (IVLCD) can result in a marked metabolic improvement in as little as seven days. However, maintenance of a IVLCD can be difficult over time and one study found that after 12 months of intensive weight management, less than half (46%) of patients were in diabetic remission. Among obese patients, the use of intermittent very-low calorie diets (500 – 600 kcal/d) for three days each week, was found to be an effective weight loss strategy. Moreover, a similar strategy, using a IVLCD for two days per week has been successfully used in patients with type 2 diabetes.
Nevertheless, the optimal IVLCD for those with type 2 diabetes remains to be determined and this led a team from the Division of Endocrinology and Metabolism, Chulalongkorn University, Thailand, to compare different protocols of IVLCD among those with type 2 diabetes. The team undertook a randomised controlled trial that compared the impact of a two-day/week and a four-day/week IVLCD versus a control group, on glycaemic control and diabetes remission in a group of obese type 2 patients. Included patients were between 30 and 60 years of age and with type 2 diabetes diagnosed within the last 10 years. Enrolled patients had a body mass index (BMI) > 23 and a HbA1c level between 6.5 and 10%. Individuals were then randomised to either the two, or four-days/week IVLCD arm or a control group (in which they received a normal diet of 1500 – 2000 kcal/day). The IVLCD groups had an intake of 600 kcal/day on either two or four days each week. Patients were assessed every two weeks for the duration of the study (20 weeks). The primary outcome of interest was a change in glycaemic control (glucose and HbA1c) and rate of diabetes remission, defined as a HbA1c of < 6.5% in the absence of pharmacological therapy at the end of the study.
A total of 40 participants with a mean age range of 49.6 years (73% female) and a mean BMI of 30.1 were included in the final analysis. The mean duration of diabetes was 4.9 years and the baseline HbA1c was 7.4% with 90.6% of participants prescribed metformin. There were significant reductions compared to baseline in HbA1c levels in both IVLCD groups with 64% of those in the 4-day/week and 29% in the 2-day/week achieving levels < 6.5%. Furthermore, diabetes remission was achieved in 29% of patients in both the 2-day and 4-day groups. In addition, complete withdrawal of all diabetic medication occurred in 64% of the 2 day/week group and 86% of those in the 4 day/week group. The mean reduction in BMI in the 4 day/week group was 3.6 and 2.1 kg in the 2 day/week group although this difference between the two groups was not-significant.
The authors concluded that given the similar level of diabetes remission in both groups, either would be beneficial to obese type 2 diabetic patients.
UmPhonsathien M et al. Effects of intermittent very-low calorie diet on glycemic control and cardiovascular risk factors in obese patients with type 2 diabetes mellitus: A randomised controlled trial. J Diabetes Investig 2021
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