The National Severe Insulin Resistance Service provides a multidisciplinary NHS service for patients with severe insulin resistance and/or lipodystrophy from throughout England. The service supports both adult and paediatric patients.
The service is based at Addenbrooke’s Hospital which is part of Cambridge University Hospitals NHS Foundation Trust (CUH). The service is funded by the NHS England.
The team includes Professor Sir Stephen O'Rahilly',Dr David Savage, Dr Robert Semple, Dr Anna Stears and Consultant Paediatric Endocrinologists Professor David Dunger and Dr Rachel Williams, in addition to a team of specialist nurses and dietitians. There is a weekly outpatient clinic and a weekly multidisciplinary team meeting. We have onsite access to genetic screening, specialised biochemical assays and specialised radiology including liver MRI/S. We also currently have access to funded treatment options including leptin, GLP1 agonists, U500 insulin and IGF-I in selected patients.
Non-urgent advice: Referral criteria
The service is targeted at patients with lipodystrophy and/or extreme insulin resistance. The referral criteria are as follows:
- Donohue Syndrome or Rabson Mendenhall Syndrome with confirmed extreme hyperinsulinaemia*
- Clinically diagnosed lipodystrophy (generalised or partial)
- Unexplained severe insulin resistance with: BMI<30kg/m2 (BMI Z score <=+3 in children) AND acanthosis nigricans AND/OR severe hyperinsulinaemia*
*fasting insulin>150pM or peak plasma insulin on oral glucose tolerance testing >1,500pM
These rare but metabolically devastating disorders are associated with significant long-term morbidity and mortality. The purpose of the service is to improve outcomes for these patients through the following mechanisms:
- By providing a precise diagnosis wherever possible.
- By the provision of targeted specialist delivered treatment interventions including both dietary and pharmacological therapies.
- By educating patients, their relatives (where this is appropriate) and local health carers.
- By raising the profile of severe insulin resistance / lipodystrophy as a clinical problem in order to improve access to optimal care for affected patients.
Disorders of insulin signalling
In children, Donohue and Rabson Mendenhall Syndrome present in infancy and early childhood and are associated with well described clinical phenotypes secondary to mutations in the insulin receptor. Milder insulin signalling disorders may present later in childhood or adolescence with clinical features of insulin resistance such as acanthosis nigricans or clinical hyperandrogenism in girls. Alternatively they may present with type 2 diabetes, with very high insulin concentrations. A proportion of these children will have identifiable mutations in the insulin receptor.
Lipodystrophy refers to a disruption of the body’s normal ability to store excess energy as fat. It may be congenital or acquired, and can be generalised (affecting all fat stores) or partial, affecting limited areas. There is often associated hyperphagia. The clinical manifestation of partial lipodystrophy is often more marked in girls and may present with oligomenorrhea and features of clinical hyperandrogenism around puberty. Lipodystrophy is associated with clinical features of insulin resistance including acanthosis nigricans. Complications include steatohepatosis, type 2 diabetes and severe dyslipidaemia. Dietary changes to a low fat, low calorie diet are the mainstay of treatment. Specific pharmaceutical treatment options are limited but leptin therapy may be an option in carefully selected patients.
How can we help?
We are happy to accept referrals or to discuss any patients whom it is felt have severe insulin resistance and/or lipodystrophy. We can provide diagnostic (both genetic and biochemical) support in addition to access to funded treatment options including GLP1 agonists, U500 insulin, leptin and IGF-I in some patients. We also provide specialist dietetic input and diabetes nursing input. Ongoing care is usually shared closely with the referring clinician.