Obese PWS Patients at Increased Risk of Type 2 Diabetes as Adults

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Patients with Prader-Willi syndrome (PWS) are at increased risk of developing type 2 diabetes mellitus as they transition into adulthood, particularly if they are severely obese and/or undergoing rapid weight gain, according to a recent study.

“These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose [sugar] monitoring during the transition period,” the researchers wrote.

The study, “Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients,” was published in the Journal of Clinical Medicine.

PWS is a genetic disorder characterized by multiple developmental, nutritional, endocrine, metabolic, and behavioral issues that manifest over the course of a patient’s lifetime. Obesity and type 2 diabetes are two conditions often associated with PWS.

Indeed, it is estimated that type 2 diabetes affects 20–25% of adults with PWS, compared with 5–7% of the general population. And data show that obesity, and its related complications, are the most common cause of death in PWS.

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Research, however, suggests that the disease mechanisms behind diabetes in PWS may be different than those seen in common obesity.

Now, researchers in France investigated the occurrence of type 2 diabetes in adolescents and young adults — patients younger than age 25 — with PWS, and tried to identify factors associated with the disease that could potentially help in the detection and prevention of early diabetes.

In total, the team examined 39 patients followed in the French PWS Reference Center network, in which data were collected between July 2020 and April 2021. The group members ranged in age from 13.9 to 47.7 years, with a median age of 25.6 years; 56.4% of the patients (22) were female.

All patients had a genetically confirmed PWS diagnosis, which had been made at a median age of 29 months, or roughly 2.5 years old. They also had a diagnosis of type 2 diabetes mellitus before the age of 25. At the time of the study, the patients had a median duration of diabetes of 9.9 years.

Concerning obesity, most patients had been classified as severely so. Starting at age 15, most patients had a body mass index or BMI — a measure of body fat based on height and weight — consistently over 30 kilograms per body square meter (kg/m2), a value that is indicative of obesity. Of note, normal BMI generally ranges from 18.5 to 24.9, with overweight classified as values of 25 to 29.9; scores 30 and high are considered obese.

Between ages 15 and 20, as they transitioned from childhood to adulthood, these patients had experienced a median 6-point gain in BMI, indicating an extreme increase in body mass and fat.

Notably, weight and diabetes were issues for the patients’ family members as well.

Type 2 diabetes had been diagnosed in at least one parent for more than one-third of the patients, while more than half of these individuals’ parents were overweight or obese.

“The prevalence of both T2DM [type 2 diabetes] (34.5%) and overweight (53.6%) was higher among the parents of our patients than what is usually described in the general population,” the researchers wrote, adding that these results “suggest that a family history of T2DM  warrants close monitoring to detect the early onset of T2DM in this population — particularly during the transition period.”

The median age at the diabetes diagnosis was 16.8, with a range from 11 to 24 years. On average, the patients’ fasting blood glucose (blood sugar levels) was 7 millimol per liter (mmol/L), whereas a normal level is under 5.6 mmol/L.

Additionally, at diagnosis, the patients’ median HbA1c — a measure of hemoglobin with attached glucose (sugar), which is indicative of average blood glucose (sugar) levels — was 8.9%. Normal HbA1c range is between 4% and 5.6%.

All patients were taking a median of one anti-diabetic medication at diagnosis, and three at the last follow-up, according to the researchers.

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A majority of patients, 70.3%, needed treatment with insulin from the time of their diabetes diagnosis. Eight had to continue insulin treatment after the age of 18 and into adulthood, “which reflects both the severity of their diabetes and the difficulty of managing these patients with oral antidiabetic drugs alone,” the researchers wrote.

“In most cases, the diabetes was difficult to control, with great inter-individual variability in HbA1c and fasting blood sugar,” the team added, noting that “this further suggests that diabetes in young patients with PWS is a somewhat atypical T2DM.”

Endocrine co-existing diseases were comparable between the diabetic patients and the general PWS patient population. However, there was an increase in metabolic and psychiatric co-existing conditions, with 47.4% of the patients being treated with antipsychotic medications at the time of the study.

“In general, patients with severe behavioral problems or psychotic disorders are more difficult to manage in terms of diet, resulting in poor weight control,” the researchers wrote. “Moreover, the antipsychotic treatments often prescribed in these cases may worsen the weight gain and metabolic syndrome and contribute to the development of T2DM.”

The team also looked at differences between PWS patients treated with growth hormone during childhood in comparison with those who were not. No significant differences in BMI and metabolic complications were found between the 21 patients treated with growth hormone and the 15 untreated patients.

Overall, based on the results, the team concluded that “patients with PWS who are at risk of developing early T2DM are those who are severely obese — especially those undergoing rapid and uncontrolled weight gain in adolescence, and this is independent of whether or not they have been treated with GH [growth hormone].”

“Adolescents with obesity and severe comorbidities [co-existing diseases], both psychiatric and metabolic, and/or a parental history of overweight or T2DM [type 2 diabetes mellitus], should be monitored closely for glucose metabolism, particularly when their BMI increases rapidly,” the team added.