Media Release: 27 August 2014
A Sydney endocrinologist worked with genetics of lipodystrophy experts in Cambridge to solve a mysterious case of diabetes from the past.
Professor Lesley Campbell, Director of Diabetes Services at St Vincent’s Hospital and a senior member of the Diabetes and Obesity Clinical Studies group at Sydney’s Garvan Institute of Medical Research has always believed that the clinic and the laboratory should be as closely allied as possible.
So when a patient was referred to her 15 years ago with a very puzzling group of symptoms, she had the foresight to take all the measurements and biopsies she could (freezing blood, tissue and fat samples) in the hope that one day new technologies would enable her to diagnose the condition.
That day came a couple of years ago when a team from the Metabolic Research Laboratories at the University of Cambridge, led by Dr David Savage, teamed up with Professor Campbell to identify the genetic anomalies underlying the case.
The patient Professor Campbell saw in 1998 was a 41 year old woman with a ten-year history of type 2 diabetes complicated by damage to the retina (diabetic retinopathy), extremely high triglycerides that were causing recurrent pancreatitis, non-alcoholic fatty liver disease, hypertension and increasingly prominent muscles which were relatively weak. Despite taking unusually high doses of insulin (over 500 units daily), the woman’s diabetes was poorly controlled.
The patient’s daughter and eldest son suffered from a similar condition, and although Professor Campbell did not treat the daughter, she received permission to take blood and tissue samples.
It was obvious that members of the family suffered from a heritable form of lipodystrophy (a rare cluster of disorders, associated with metabolic syndrome, that feature unusual body composition).
Professor Campbell recommended in 2005 that the mother undergo ‘Roux-en-Y’ gastric by-pass surgery – which had a remarkably curative effect. She lost 20 kg, her insulin requirements dropped from 500 to 100 units per day, her triglyceride profile improved and her heart health improved dramatically.
The patient’s daughter also had the surgery with even more remarkable results - a 55 kg weight loss and no further need for insulin.
The Cambridge team identified a mutation in the perilipin-1 gene in both mother and daughter. Mutations in this gene affect the storage of fats in fat cells, a very important feature of normal metabolism. The findings are described in the journal Diabetes, now online.
“In addition to throwing light on the importance of perilipin, this project also generated interesting data about the gut hormone GLP1, which creates a feeling of fullness after a meal,” said Professor Campbell.
“GLP1 happens to be in vogue at the moment – as one of the gut hormones that might help us fight obesity.”
“I measured GLP1 in my patient, both before and after surgery, and levels of GLP1 went up after surgery.”
“I hypothesise that these higher levels of GLP1 might have helped my patient respond so well to surgery.”
“While cases such as these are very rare, it is very important to put them on the record, to help clinicians identify similar syndromes in the future – and to suggest new courses of treatment.”