Health condition
Severe insulin resistance syndromes
Severe insulin resistance syndromes - from insulin receptor gene defects to type B insulin resistance caused by anti-receptor antibodies - produce extreme insulin requirements, acanthosis nigricans and ovarian hyperandrogenism, and need specialist diagnosis.
Why trust this guide
- 01
Editorial team
Written by our editorial team from the UK sources listed on each page.
- 02
Sourced from guidance
Checked against current NHS and UK specialist society guidance at the time of review.
- 03
Current for 2026
Reviewed on 2026-09-27 with the next review scheduled for 2027-09-27.
Key facts
The essentials at a glance.
The symptoms to recognise, when to seek help, which specialist to see, and what treatment usually involves.
-
Hallmarks: acanthosis nigricans (velvety darkened skin folds), insulin requirements in the hundreds or thousands of units, and severe PCOS-type features in women
-
Causes span receptor gene defects (including Donohue and Rabson-Mendenhall spectrum), lipodystrophies, and acquired type B insulin resistance from autoantibodies
-
Type B insulin resistance often arrives abruptly in middle age, frequently with lupus or other autoimmunity, and can swing to severe hypoglycaemia
-
Workup: fasting insulin and C-peptide, leptin and adiponectin, lipid pattern, fat distribution assessment, antibody testing and genetic panels
-
National severe insulin resistance services exist (Cambridge leads in the UK) and accept referrals
Understanding the condition
What it is and what happens next.
What causes it, how it is diagnosed, and the treatment routes available in the UK.
What it is and how it feels
When insulin cannot deliver its message, the pancreas shouts - levels climb ten- and hundred-fold, staining skin folds dark, driving ovaries to overproduce androgens, and eventually failing to hold glucose at all. The syndromes differ in machinery: inherited receptor defects declare themselves early and run on a spectrum of severity; lipodystrophy starves the signal of its target tissue; and in type B disease, autoantibodies blockade the receptor directly, producing some of the most extreme diabetes ever measured, oddly interspersed with dangerous hypoglycaemia.
Diagnosis and treatment routes
Precise diagnosis changes treatment fundamentally: receptor defects may respond to IGF-1-based therapy, lipodystrophy to metreleptin, and type B disease to rituximab-based immunosuppression that can achieve full remission. The screening biochemistry - paired insulin, adiponectin, leptin - is inexpensive and points the way, with genetics and antibody studies confirming. Anyone injecting vast insulin doses with little effect deserves referral to a severe insulin resistance service; a private endocrinology review to start that pathway is typically available within about two weeks.
Seeing a specialist
Who to see, and how quickly you can be seen.
The specialist for this condition is usually a consultant endocrinologist. Your GP can refer you on the NHS, or you can arrange a private consultation directly.
A quiet reminder
This guide is for information, not medical advice.
Your GP knows your history and can tell you which parts apply to you. If in doubt, see them - and seek urgent care for any of the emergency symptoms described above.
Frequently asked
Common questions about Severe insulin resistance syndromes.
Quick, plain-English answers to what people ask us most.
-
What are severe insulin resistance syndromes?
Severe insulin resistance syndromes - from insulin receptor gene defects to type B insulin resistance caused by anti-receptor antibodies - produce extreme resistance to insulin's normal effects, requiring specialist recognition and management distinct from typical type 2 diabetes.
-
What causes severe insulin resistance syndromes?
Causes include specific genetic mutations affecting the insulin receptor, and in type B insulin resistance, antibodies that attack the insulin receptor directly, often occurring alongside other autoimmune conditions.
-
What are the symptoms of severe insulin resistance?
Symptoms include very high blood sugar resistant to standard treatment, dark, thickened skin patches (acanthosis nigricans), and in women, features of excess androgen such as irregular periods and excess hair growth.
-
How is severe insulin resistance treated?
Treatment often requires very high doses of insulin or specific medications targeting insulin resistance, and for type B insulin resistance, immunosuppressive treatment aimed at the underlying antibody-driven process.
-
Is severe insulin resistance dangerous?
Yes, it can cause very difficult-to-control blood sugar with associated long-term complications, so specialist endocrine input is important for optimal management.
-
Severe insulin resistance vs typical type 2 diabetes - what's the difference?
Type 2 diabetes involves relative insulin resistance manageable with standard treatments, whereas severe insulin resistance syndromes involve a much more extreme resistance requiring specific diagnosis and often very different, more intensive treatment approaches.
-
When should I see a specialist about severe insulin resistance?
See a doctor if diabetes is very difficult to control despite high-dose standard treatment, so specific causes can be investigated. A private consultant endocrinologist can typically be seen within about two weeks.