In PWS, Body Weight, Genetics May Predict Success in Weight Reduction


Adults with Prader-Willi syndrome (PWS) who weigh more, have a higher body mass index (BMI), and have a larger waist and hip circumference are most likely to respond successfully to a multidisciplinary weight reduction program, according to a single-center , six-year study in Italy.

In addition, having PWS caused by the deletion of paternal genes on chromosome 15 — the most common cause of the disease — was associated with a higher chance of responding to the program.

These findings highlight potential predictors of patients’ responses to weight reduction programs, the noted researchers. They also may help identify those at higher risk of failure — and may aid in the development of tailored programs for such patients.

“PWS patients are considered quite resistant to interventions aimed at weight loss and a relatively small percentage of these patients succeed in obtaining from these interventions,” the researchers wrote. “It is consequently important to understand the possible predictive factors of responsiveness (or non) to long-term body weight (BW) loss programs.”

Future, larger studies are needed to confirm these results.

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The study, “Predictive factors of responsiveness to a body weight reduction program in Prader–Willi patients at 6 years of follow-up,” was published in the journal Scientific Reports.

A genetic disease, PWS is caused by the loss of function of genes located on the paternally inherited chromosome 15. These genes control appetite, metabolism, growth, intellectual function, and social behavior.

The most common cause of the disease is a deletion of this region, called del15. Following that, the inheritance of two copies of chromosome 15 from the mother rather than one from each biological parent — a condition dubbed maternal uniparental disomy, or UPD — is a second main cause.

PWS is characterized by “early poor feeding and lack of appetite, followed by uncontrolled appetite and lack of satiety that cause obesity, mostly after the age of 2–3 years,” the researchers wrote.

People with PWS also show lower muscle mass relative to obese people without the disease, meaning that they have an even lower energy expenditure at rest.

As such, according to researchers, “a multidisciplinary approach including food restriction, physical rehabilitation, and psychological counseling is essential in PWS patients in order to improve body composition and quality of life.”

Now, a team in Italy retrospectively evaluated the efficacy of a six-year multidisciplinary metabolic rehabilitation program in 60 adults — 38 women and 22 men — with PWS. All were seen at a single center in Italy.

The researchers also analyzed whether any demographic or clinical factors at the study’s start (baseline) could predict long-term responses to the program.

The weight reduction program consisted of three in-hospital periods: at the study’s start, at three years, and at six years.

Each period comprised three weeks of the energy-restricted Mediterranean diet in combination with physical rehabilitation — moderate aerobic activity — and nutritional information.

At the end of each period, the patients and their caregivers received individualized counseling on nutrition and physical activity. Over the six years, a multidisciplinary team monitored patients’ clinical conditions and concomitant treatments, and promoted lifestyle changes.

The patients’ mean age at the program’s start was 27, and they weighed a mean of 97 kg, or about 213.85 lbs. Their mean BMI, a measure of body fat based on weight and height, was 42; of note, values ​​above 30 indicate obesity.

The results showed that, after six years, the patients’ mean weight was reduced to 94 kg, or about 207.23 lbs, and their mean BMI to 40.

A total of 24 patients (40%) responded to the six-year program — meaning that they lost more than 5% of their body weight. Another 19 individuals (32% of patients) were considered non-responders, as they gained more than 5% of their initial weight. Weight changes within the 5% margin were detected in 17 patients (28%). These participants were considered “stable.”

Responders showed a significant reduction in body weight — by 10-17% — and BMI, by 11-18%, at three and six years, relative to the program’s start. This group also reduced their waist and hip circumferences by 6–10%, and their fat mass by 18–29%.

In the non-responder group, these parameters were all significantly increased — by up to 18%.

The fact that nearly 70% of patients showed stable or reduced body weight after the program “can be considered a ‘partial’ success’ taking into account the almost unavoidable progressive increase of BW [body weight] in these ‘resistant’ patients,” the researchers wrote.

However, it is possible, the team noted, that some of these adult patients transitioned from nutritional phase 3, characterized by insatiable hunger, to nutritional phase 4, in which patients are able to feel full again.

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When looking at potential predictors of success in weight reduction, the researchers found that responders had significantly higher BMI, and waist and hip circumferences at baseline, relative to both non-responders and stable patients.

Also, a significantly greater proportion of responders took medication for high blood pressure relative to the other two groups (29% vs. 0–12%). That was “probably as a consequence of the fact the former had higher baseline [body weight] and BMI,” the team wrote.

Notably, patients with del15 were significantly more frequent among responders (88%) than in the stable (71%) and non-responder (58%) groups.

“This could mean that a UPD patient involved in a long-term multidisciplinary BW program has lower probability to respond positively, thus requesting a more careful tailoring of the program itself,” the researchers wrote.

Notably, PWS caused by UPD has been associated with a higher risk of psychotic-type illnesses and autism. That can challenge patients’ adherence to this type of long-term program, “in which one of the main purposes is to improve lifestyle,” the team added.

No other group differences were detected in terms of baseline metabolic and blood parameters, smoking status, diabetes, or use of anti-diabetic medication. Growth hormone therapies or other hormonal medications also did not result in any differences in the parameters.

These findings highlight the relatively high efficacy of a six-year multidisciplinary weight reduction program and suggest ways to identify patients more or less likely to respond to such programs.

“Additional studies are mandatory to quickly adapt the BW reduction programs to the individual characteristics of the single PWS patient in a better way,” the team wrote.

Larger studies — including ones that also take into account socioeconomic factors, mental/emotional status, and detailed information on diet and physical activity outside of the hospitalizations — are needed to confirm these findings.

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