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Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of March 2022.
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Prof. Aartsma-Rus reads and comments on the paper titled: BMI-z scores of boys with Duchenne muscular dystrophy already begin to increase before losing ambulation: a longitudinal exploration of BMI, corticosteroids and caloric intake.
Today’s pick is from Journal of Neuromuscular Diseases by Houwen-van Opstal, a Duchenne Center NL collaboration on obesity development in Duchenne patients based on longitudinal analysis. Doi 10.1016/j.nmd.2022.01.011
Duchenne patients lose muscle tissue and function and therefore are progressively less active. Due to decreased exercise they are at risk of becoming obese. Studies have reported >50% of Duchenne patients being obese at the age of 10.
Of course Duchenne patients also chronically are treated with corticosteroids, which increases appetite and further increases the risk for obesity. However, also >50% of Duchenne patients not using corticosteroids are obese.
Obesity involves multiple health risks, but for Duchenne patients there are additional negative effects: it further impedes movement, reduces the effectiveness of orthopedic surgery, and increases the speed of development of respiratory insufficiency and heart pathology
Authors here wanted to study the impact of ambulatory status, transition from ambulatory to non ambulatory, caloric intake and steroid use on obesity. They use the BMI z-score (a z-score is a measure for how much something differs from the expected / average).
The study was done retrospectively with 159 Dutch Duchenne patients & covered 790 hospital visits (on average 4-5 annual visits/patient). 95 patients were ambulatory at the first visits. Most patients were on steroids – in the Netherlands generally an intermittent regimen is used
44% of ambulant patients were overweight vs 51% of non-ambulant patients. The caloric intake of the whole group was 156 kcal/day more than the recommended intake. In the non-ambulant patients there was a correlation between intake and BMI z-score (more intake, higher BMI)
Corticosteroid use did not influence the BMI. Notably, BMI z-scores were very variable, but it was clear that before loss of ambulation and during loss of ambulation BMI z-scores increased (in 7-12 year old patients).
When patients became non-ambulant caloric intake decreased, but often was still higher than the individually recommended intake. Authors discuss the limitations of the study. Using BMI as a measure for obesity for Duchenne is controversial as their body composition is changed.
Muscle tissue will be replaced by fat – which also reduces the basic energy expenditure (it takes more energy to maintain muscle than fat even if you do not use it). The challenge with using weight is that many Duchenne patients have reduced stature – due to steroids and Duchenne
One needs to compensate for that & BMI does this. Another challenge is measuring height in non ambulant patients. Authors use the ulna method (measuring the length of the forearm and extrapolating this to height). They indicate that ideally this is started in ambulatory patients
Monitoring food intake is challenging (this is based on intake in the past 48 hours) and it is known that there often is underreporting (I would have a hard time remembering my intake over the past 48 hours – likely would forget things). With food diaries this can be improved.
Authors indicate that knowing the BMI/weight will increase especially between 7 and 12 years, risking overweight and that it starts to increase when boys become non-ambulatory (process that can take years), ideally, caloric restrictions start early to prevent overweight
Interestingly no effect of steroid use was seen on overweight. However, only a few patients were not on steroids and an intermittent regimen is used in the Netherlands. Would be interesting to see a similar analysis in patients on a daily steroid regimen.
Authors stress that it is crucial to have a dietician in the multidisciplinary care team to provide individualized recommendations on caloric intake from an early age. I agree – it is difficult to lose (over)weight for anyone, but for Duchenne patients even more so.
This is due to the reduced activity but also because of specific needs related to the ongoing muscle damage. Specialized dieticians are needed here. I commend the authors for this study & the publication.
Disclaimer: Prof. Aartsma-Rus is part of Duchenne Center NL (but was not part of this study)
Pictures by Annemieke, used with permission.
Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).
Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.
In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.
