Incretin therapy in prader willi syndrome

Incretin therapy in Prader Willi syndrome
Successful treatment of obesity and diabetes mellitus with incretin analogue over 3 years in an adult with Prader Willi syndrome.
Paisey RB, FRCP; Lawrence C, MB; Bower L, BSc; Rosindale S, MA.
Torbay Hospital, South Devon Healthcare NHS Foundation Trust

Incretin therapy in PraderWilli syndrome
The syndrome:
Described in 1956 by Andrea Prader, Heinrich Willi, Alexis Labhart, Andrew Ziegler, Guido Fanconi.
Paternal genes on Chromosome 15 (q11-13)
absent or not expressed.
Between 1:25,000 and 1:10,000 live births
Floppy baby, reduced IQ, hyperphagia, hypogonadism, some deaths from hypoxia, infections and vomiting.

Introduction
Prader-Willi syndrome (PWS) is associated with morbid obesity and an increased propensity for early development of type 2 diabetes. It is inferred that this is related to hyperphagia and severe obesity though beta cell function is reduced

Incretin analogue therapy :-
Success in weight reduction and improvement in glycaemia in type 2 diabetes.
BUT considered most effective in insulin resistant subjects and can cause nausea and vomiting.

A 36 year old female with Prader Willi syndrome living in sheltered accommodation presented with right hemiparesis and dysphasia.
She had never received growth hormone therapy, nor estrogenic hormones. She had developed type 2 diabetes 10 years previously.
Genetic confirmation of the diagnosis had been made in childhood (46, XX.ish del (15)(q11.2q11.2)(SNRPN-)).

Treatment from diagnosis of diabetes 1998
Nutrition management by a carer, regular walks and escalation of oral hypoglycaemic agents
(Metformin, Gliclazide, and Rosiglitazone)
Statins introduced 2000
+vemicroalbuminuria 2001-Ace inhibitors
Heavy smoker

Progress on initial therapies 2000-2007
Weight increased from 72 to 78 Kg and blood pressure from 130/80 to 150/90 mmHg,HbA1c 13% . Hyperphagia intense.
Biphasic insulin was added to control osmotic symptoms 6 months before admission and Rosiglitazone stopped.
This resulted in further weight increase to 83 Kg (BMI 33) Hba1c 10.4%.....STROKE!!

Figure 1 CT scan after sudden right sided weakness in 36 year old patient with Prader Willi Syndrome

Progress after stroke:-
After a complete recovery from the stroke her craving for sweet foods especially cakes and confectionary and poor metabolic control of diabetes persisted.
Discussions with the patient, her carer and mother established that she had capacity to consider treatment with incretin analogue in addition to Insulin Metformin and Gliclazide.

Progress on Exenatide:-
Five micrograms twice daily Exenatide was commenced increased to 10 micrograms twice daily after one month as nausea had only been transient.
During the first 6 months of incretin therapy insulin was reduced and then withdrawn due to improvement in well being, reduction in hyperphagia and loss of weight to 71.3 Kg. Waist circumference had decreased from 120 to 115 cm, HbA1c to 10%.

Progress leading to stroke 2005-2007

Incretin therapy in PraderWilli syndrome
It’s given me my life back!

Safety issues during 4 yrs therapy:
Patient has remained on statins and ace inhibition from diagnosis of diabetes
Blood pressure improvement 130/80 mmHg has been sustained (150/95 mmHg at time of stroke)
Background retinopathy stable
Occasional nausea only

Incretin therapy in Prader Willi syndrom
The condition is considered to exhibit low metabolic rate and an hypothalamic cause of increased appetite, with no evidence of increased insulin resistance
In this case study incretin analogue therapy has been associated with remission in hyperphagia, obesity and hyperlipidemia and substantial improvement in diabetes control also permitting withdrawal of insulin and sulphonylurea.

There is a concern that food binges may provoke severe vomiting with incretin analogues .
The success of this therapy in our case gives rise to cautious optimism that other adults with Prader Willi syndrome and glucose intolerance might benefit from incretin analogue therapy.
A clinical trial would be justified with very careful monitoring of eating behavior

The next step
Adult Patients with PraderWilli Syndrome in Paignton, Wigan, Plymouth, Gloucester, all with poorly controlled diabetes and obesity.
To compile a case series.....

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Incretin therapy in prader willi syndrome

by PeninsulaEndocrine on Aug 12, 2011

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