Diabetes Finding in PWS Patient Underscores Need for Antibody Testing

The case of a woman with Prader-Willi syndrome (PWS) who developed slowly progressive insulin-dependent diabetes mellitus, or SPIDDM —  usually type 2 diabetes in adults — underscores the need to test patients for disease-causing antibodies and genetic markers, a Japanese study reports.

Titled “A Case of Prader-Willi Syndrome with Slowly Progressive Insulin-dependent Diabetes Mellitus,” the case report appeared in the journal Internal Medicine.

PWS is characterized by skull and facial abnormalities, decreased muscle tone in infants, intellectual disability, and hypogonadism, or the impairment of the sex glands.

Excessive appetite and obesity also are hallmarks of the disease. Obesity related to PWS can lead to insulin resistance — when cells do not respond well to insulin — and abnormal blood glucose or blood sugar levels.

SPIDDM, also referred to as latent autoimmune diabetes, generally presents as type 2 diabetes in adults, according to the researchers. It is characterized by the early presence of at least one disease-associated autoantibody — antibodies that mistakenly attack the body’s tissue. Typically, islet cell autoantibodies and/or glutamic acid decarboxylase autoantibodies (anti-GAD) are detected early after SPIDDM onset and are undetectable later.

The researchers noted that this case study is the first to describe a person with both PWS and SPIDDM. The patient, a 52-year-old Japanese woman, had a history of muscle weakness as an infant and facial abnormalities, obesity, intellectual disability, and hypogonadism as a child. She was diagnosed with diabetes at age 23.

The woman was admitted to the hospital five years later due to decreased glucose tolerance. Based on her clinical features and a deletion in chromosome 15 known to cause PWS, she was diagnosed with the disease and subsequently began hypoglycemic treatment to lower blood glucose levels. 

Yet, her glucose levels continued to worsen and she was occasionally re-admitted to the hospital for treatment.

At age 42, the woman’s condition worsened and became unstable. Her urine levels of C-peptide immunoreactivity (CPR) had decreased to 23.3 micrograms (mcg)/day while blood CPR was at 0.68 ng/mL, indicating insufficient insulin levels. The hypoglycemic treatment was terminated and an insulin injection therapy initiated. 

The patient was hospitalized two years later with even more severely diminished insulin secretion capacity. She began intensive insulin therapy but six years into the treatment, at age 50, her urine and blood CPR levels had dropped further. At this point, anti-GAD antibodies were detected at a concentration of 5.2 units (U)/mL, above the normal range of less than 1.5 U/mL. 

Found to be obese, her blood glucose and HbA1c levels — both measures of blood sugar — were higher than normal at 203 mg/dL (glucose) and 11.2% (Hba1c). Her anti-GAD antibody level of 1.6 U/mL was slightly above the normal range, while CPR was even lower.

CPR response testing revealed signs of insulin dependence. Her HLA haplotype, which denotes genetic variations key for immune system recognition of the body’s own proteins, was a genetic risk factor for both type 1 diabetes and SPIDDM. Due to her initial insulin-independence stage and anti-GAD levels, the patient was diagnosed with SPIDDM. 

The researchers say this patient’s case highlights the need for testing people with PWS and other symptoms for disease-causing antibodies and genetic markers.

“When a patient has a risk-associated HLA haplotype and shows a progressive reduction in insulin secretory capacity, an association with SPIDDM should be considered, even in patients with PWS,” the scientists wrote. “If a patient is diagnosed with SPIDDM, even if they have underlying PWS, intensive insulin therapy should be started.”