Growth hormone for PWS may increase diabetes risk, study finds
Researchers say patients should be monitored for symptoms
Long-term treatment with human growth hormone, also known as somatropin, does not seem to influence mortality in people with Prader-Willi syndrome (PWS), but may increase the risk of developing type 2 diabetes, a study from South Korea found.
The risk of type 2 diabetes increased by 6% with each additional year of treatment. Other factors, including co-occurring conditions (comorbidities), were also significantly linked to a higher risk of developing the condition. Comorbidities were also significant predictors of death.
The researchers said the results highlight the importance of monitoring PWS patients on growth hormone therapy (GHT) for signs of diabetes and other conditions.
“A multidisciplinary approach—including endocrinology, nutrition, behavioral management, and psychosocial support—remains essential to optimizing outcomes in patients receiving GHT,” they wrote.
The study, “Long-term impact of growth hormone therapy on mortality and type 2 diabetes in Prader–Willi syndrome: a nationwide cohort study,” was published in Frontiers in Endocrinology.
Scant ‘population-based’ evidence on widely used treatment
PWS symptoms include muscle weakness, slow growth, excessive hunger, and behavioral problems. Most PWS patients have deficient levels of growth hormone, which regulates several biological processes, including growth, body composition, and metabolism of blood sugar and fats.
Treatment for PWS primarily focuses on controlling symptoms and improving quality of life. GHT, a standard PWS treatment, is sold in the U.S. under brand names including Genotropin and Norditropin, among others, with biosimilars available.
“Although growth hormone therapy … is widely used as standard care, population-based evidence on its long-term safety, particularly in relation to mortality and type 2 diabetes … remains limited,” the researchers wrote.
Type 2 diabetes occurs when the body becomes resistant to insulin, a hormone that helps regulate blood sugar levels, and the inability to produce enough insulin results in elevated blood sugar. Because growth hormone plays a role in blood sugar regulation, GHT can counteract the effects of insulin.
“We hypothesized that prolonged exposure to GHT may be associated with altered risks of mortality and [type 2 diabetes] in individuals with PWS,” the researchers wrote.
To test their hypothesis, the team analyzed 2005-2023 data from the Korean National Health Insurance Service, which covers 97% of the country’s population. Based on diagnostic codes and medication history, they identified 385 people with PWS who received an approved GHT.
These participants were a median of 1 year old when they were diagnosed with PWS, and started GHT at a median age of 2, the typical age of initiation in South Korea. At diagnosis, 2.6% of participants had type 2 diabetes. By the most recent follow-up, at a median age of 11, that rate had risen to 14.8%.
Many patients had developed comorbidities by the time of their last follow-up, with chronic lung disease as the most common (92.7%). About one-quarter of participants (27.5%) had mild liver disease — though moderate or severe liver disease was rare (0.5%) — and a similar proportion (26.5%) had behavioral disorders.
Statistical analyses adjusted for potential influencing factors showed that GHT duration was a significant risk factor of type 2 diabetes, with each year of treatment with GHT corresponding to a 6% increase in risk.
While age at diagnosis and at most recent follow-up were also tied to risk, the strongest predictors were specific comorbidities. Peptic ulcer disease, mild liver disease, and diabetes insipidus were associated with a four to seven times higher risk of type 2 diabetes.
Peptic ulcer disease is characterized by sores in the digestive system, and diabetes insipidus is a rare disorder that causes the body to make too much urine.
When the researchers examined risk factors for death, GHT duration didn’t emerge as a significant predictor. Instead, the analysis suggested “that mortality in this population is more closely associated with comorbidities … than with GHT itself,” the researchers wrote.
Behavioral disorders, adrenal insufficiency, kidney disease, and conditions affecting blood vessels outside of the heart were significantly linked to a 10- to 30-fold higher mortality risk. Adrenal insufficiency is a disorder where the adrenal glands don’t produce enough essential hormones.
These results suggest that long-term GHT may be linked to a higher risk of developing diabetes in people with PWS. Specific comorbidities were also risk factors for type 2 diabetes and for death.
The study could only detect potential links, not establish cause-and-effect associations between GHT and type 2 diabetes, and studies following patients over time are needed to clarify the long-term effects of GHT, the researchers said.
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