# Lipodystrophy and Insulin Resistance Syndromes

> Lipodystrophy and insulin resistance syndromes for NEET-PG Medicine: congenital and acquired forms, leptin deficiency, insulin resistance types and metreleptin.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/lipodystrophy-and-insulin-resistance-syndromes
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Harrison's Principles of Internal Medicine; Williams Textbook of Endocrinology; ADA Standards of Care in Diabetes
- How to cite: "Lipodystrophy and Insulin Resistance Syndromes", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/lipodystrophy-and-insulin-resistance-syndromes

## Direct answer

Lipodystrophy is a group of disorders in which adipose tissue is lost, generally or partially, and this causes severe insulin resistance, hypertriglyceridaemia, fatty liver and diabetes. Generalised forms cause leptin deficiency, which drives hyperphagia and metabolic disease. Metreleptin, a recombinant leptin, is licensed for leptin deficiency in generalised lipodystrophy. Severe insulin resistance syndromes, types A and B, are separate conditions in which body fat is normal.

## What you must remember

- **Congenital generalised lipodystrophy:** autosomal recessive near-total absence of fat, with muscular prominence, acanthosis, hepatomegaly and very high triglycerides.
- **Familial partial lipodystrophy:** loss of limb and gluteal fat with fat accumulation on the face and neck, and the Dunnigan type is linked to LMNA mutations.
- **Acquired generalised lipodystrophy:** diffuse subcutaneous fat loss, often following autoimmune panniculitis or autoimmune disease; HIV antiretroviral lipodystrophy is a separate pattern of limb lipoatrophy with central fat gain.
- **Acquired partial lipodystrophy:** Barraquer-Simons syndrome, with upper body fat loss, linked to complement C3 nephritic factor.
- **Leptin deficiency:** leptin is produced by adipose tissue to signal satiety, so its loss causes hyperphagia, insulin resistance and hypogonadism.
- **Metreleptin:** recombinant leptin for leptin deficiency in generalised lipodystrophy, with a boxed warning for lymphoma and anti-metreleptin antibodies.
- **Insulin resistance types:** type A is due to insulin receptor or signalling defects in young women with hyperandrogenism, while type B is caused by insulin receptor autoantibodies, often in systemic lupus erythematosus.

## How the syndromes differ by fat distribution

Lipodystrophies are classified mainly by where fat is lost and whether the loss is generalised or partial. The table below groups the syndromes in a way that helps with recall in examinations. Recognising the pattern first narrows the search for the genetic or autoimmune cause.

| Syndrome | Fat pattern | Key association |
|---|---|---|
| Congenital generalised | Near-total fat absence | Hepatomegaly and very high triglycerides |
| Familial partial | Limb and gluteal loss, neck and face gain | LMNA mutation in the Dunnigan type |
| Acquired generalised | Diffuse subcutaneous loss | Autoimmune disease or panniculitis |
| Acquired partial | Upper body fat loss | Complement C3 nephritic factor |
| Insulin resistance type A | Normal fat | Young women with hyperandrogenism |
| Insulin resistance type B | Normal fat | Insulin receptor autoantibodies, often in SLE |

The table shows that fat distribution, rather than the amount of fat alone, separates the lipodystrophies. The insulin resistance syndromes keep a normal fat mass, so their metabolic picture is driven by receptor or antibody defects rather than by adipose loss. A patient with generalised fat loss therefore needs screening for leptin deficiency and fatty liver, whereas a patient with normal fat and hyperandrogenism needs assessment for receptor defects.

## Where the exam tries to catch you

Lipodystrophy questions usually test the leptin link, the metreleptin indication or the difference between fat loss and obesity.

- **Trap:** equating lipodystrophy with obesity. — **Correct:** lipodystrophy is loss of fat, and it causes severe metabolic disease even when body weight is normal or low.
- **Trap:** prescribing metreleptin for common obesity. — **Correct:** it is indicated for the complications of leptin deficiency in generalised lipodystrophy, and obesity without leptin deficiency does not qualify.
- **Trap:** treating lipodystrophy diabetes with insulin alone. — **Correct:** insulin resistance is severe and hypertriglyceridaemia persists, so metreleptin is considered in generalised leptin deficiency.

## Frequently asked questions

### Why does leptin deficiency cause hyperphagia in generalised lipodystrophy?

Leptin is produced by adipose tissue and signals satiety to the hypothalamus. Leptin deficiency in generalised lipodystrophy removes this satiety signal, which causes hyperphagia and worsens insulin resistance. Metreleptin replaces the missing hormone to correct these effects.

### Which lipodystrophy is linked to LMNA mutations?

Familial partial lipodystrophy of the Dunnigan type is linked to LMNA mutations and is inherited in an autosomal dominant pattern. It causes loss of limb and gluteal fat with fat accumulation on the face and neck. Severe insulin resistance and hypertriglyceridaemia are typical features.

### What warnings apply to metreleptin therapy?

Metreleptin carries a boxed warning for anti-metreleptin antibodies, which can neutralise the drug, and for lymphoma. Patients need monitoring for antibody formation and for lymphoma during therapy. The drug is restricted to generalised lipodystrophy with leptin deficiency, as stated in its labelling.

### How does type B insulin resistance differ from type A?

Type B insulin resistance is caused by autoantibodies against the insulin receptor, often in autoimmune conditions such as systemic lupus erythematosus. Type A is due to receptor or signalling defects and is seen mainly in young women with hyperandrogenism. Type B can also cause hypoglycaemia through agonist antibody activity.