Lipodystrophy

Lipodystrophy is a condition in which the amount and/or distribution of adipose tissue (fat tissue) in the body is abnormal. Different types of lipodystrophy cause loss or re-distribution of fat tissue in different patterns.

What is Lipodystrophy?

Lipodystrophy is a condition in which the amount and/or distribution of adipose tissue (fat tissue) in the body is abnormal. Different types of lipodystrophy cause loss or re-distribution of fat tissue in different patterns. Adipose tissue is very important because it stores the energy (calories) that we consume as triglyceride (a type of fat). It makes hormones which help control how much you eat and how your body burns energy. In people with lipodystrophy the ability of adipose tissue to store energy from the diet as a type of fat called triglyceride is reduced involving either the entire body or just certain areas like arms and legs. The body must find another organ in which to store this fat. The storage of fat in other organs is known as ‘ectopic fat’. The liver, muscle and pancreas are the organs that most often store ectopic fat. Ectopic fat may cause several metabolic complications including diabetes with severe insulin resistance (reduced ability to respond to insulin), high blood triglyceride-levels, fatty liver disease and liver inflammation, and subfertility. These complications impact on the health of those affected. The severity of these metabolic problems are often related to the extent of fat loss. Lipodystrophy illustrates the critical role of adipose tissue in maintenance of metabolic homeostasis (energy balance in the body).

How common is Lipodystrophy?

Lipodystrophy is a rare disease. Worldwide, the reported prevalence is 4.7 cases per million, but this is probably an underestimate. It is most frequently diagnosed in females. However, it is unlikely that lipodystrophy affects more females than males, rather it is more easily diagnosed in females where changes in adipose tissue distribution are more obvious.

What causes Lipodystrophy?

There are a variety of known causes of lipodystrophy.  These may be inherited (genetic) or acquired.

  • Inherited causes of lipodystrophy can result in a partial or complete lack of adipose tissue among those affected. Most of the genes involved appear to play a role in the development and function of adipose tissue. Inherited forms of lipodystrophy can pass from one generation of a family to the next, but the chances of this depend on the particular gene that is responsible.
  • Acquired lipodystrophy may be associated with the use of certain medications, infections, autoimmune diseases or following radiation therapy for cancer. However, in many cases, the cause is unclear. Acquired lipodystrophy can develop at any stage of life and can be partial, affecting some of the body, or more uncommonly can be generalised, affecting the whole body.

What are the signs and symptoms of Lipodystrophy?

People affected with lipodystrophy present to medical attention in a variety of ways. 

Altered appearance:

  1. Reduced fat tissue: There may be a notable absence of fat under the skin and this can be associated with the increased prominence of muscles and blood vessels. In addition to a reduction in adipose tissue there can be an abnormal increase in adipose tissue affecting certain parts of the body in people with partial lipodystrophy. Increased adipose tissue is typically seen on the abdomen (tummy), face, neck and between the shoulder blades and sometimes in the genital region of females.
  2. Skin changes: Lipodystrophy is often associated with increases in insulin production by the pancreas. This can result in changes to skin which include thickening, darkening and velvety appearance that is referred to as “Acanthosis Nigricans” and usually affects the neck and underarm. In some people with lipodystrophy an increased number of skin tags are seen.

 Metabolic disturbances:

  1. Diabetes may be the first presentation of lipodystrophy.
  2. High circulating fats in the blood, specifically increased triglycerides, are common among patients with lipodystrophy, and when severe increases the risks of inflammation of the pancreas, or pancreatitis.
  3. Hyperandrogenism/ovarian dysfunction affects many females with lipodystrophy. It refers to an imbalance of a particular group of hormones called androgens. Some patients may present with irregular or absent periods and/or hirsutism which is excess hair growth in a male pattern.  This is similar in presentation toovary-syndrome/'> polycystic ovarian syndrome (PCOS).

Causes/Forms of Lipodystrophy

Many but not all forms of lipodystrophy are inherited.  These can cause either generalised loss of fat (Congenital Generalised Lipodystrophy or CGL) or partial loss of fat (Familial Partial Lipodystrophy or FPLD). Based on the clinical findings and family history, some patients affected by lipodystrophy will undergo genetic testing. It is important to understand if the cause of lipodystrophy is genetic as this has implications for other family members, and family screening may be offered.

 

How is Lipodystrophy diagnosed?

  1. Lipodystrophy is a diagnosis based on clinical assessment.  In cases of generalised absence of adipose tissue, it is important to exclude calorie (food) deprivation or some other rare causes.
  2. Blood tests may also be carried out to measure adipose tissue hormones (adipokines) as they may be reduced in the presence of limited adipose tissue.
  3. Genetic testing may be undertaken where inherited forms of lipodystrophy are suspected.

 

How is Lipodystrophy treated?

Currently there is no specific treatment that will permanently replace adipose tissue.

  • Cosmetic

The reduced amount of adipose tissue and its impact on appearance is distressing to some people. In certain cases, cosmetic interventions and surgery have been used. The best approach to cosmetic surgery in lipodystrophy has not been formally studied.

  • Dietary

The main treatment focus in lipodystrophy is on a low fat or low energy diet. The aim of dietary therapy is to reduce the amount of ectopic fat in organs which contributes to insulin resistance and the development of metabolic complications of lipodystrophy. Dietary intervention can produce major improvements in many of the established complications that are associated with ectopic fat such as insulin resistance, high blood fat and liver inflammation.

  • Leptin

In certain types of lipodystrophy Leptin replacement therapy may be prescribed. Leptin is a hormone which is made by adipocytes (fat cells). Leptin regulates appetite. In patients affected by lipodystrophy leptin levels can be low due to the reduced number of adipocytes and when this happens it may increase appetite. Increased appetite and excess food intake will have a negative effect on metabolism. In such cases Leptin therapy can reduce appetite and improve some of the metabolic complications of the condition. It is most often used in cases of generalised lipodystrophy where there is a near absence of fat.

  • Psychological support

As a chronic condition and one that is appearance altering, lipodystrophy can be associated with psychological distress. Some patients may benefit from accessing a variety of psychological support services.

  • Medication

Where specific complications arise such as diabetes and high triglycerides in the blood, medical therapy specific to those conditions may be recommended. It is not uncommon for lipodystrophy patients with diabetes to require high doses of insulin, in that instance concentrated forms of insulin therapy or sometimes insulin pump therapy may be needed. All of these medical interventions are prescribed in conjunction with low energy/low fat diet.

  • Metabolic Surgery

Among patients with partial lipodystrophy and metabolic complications that are not adequately controlled using conventional therapy, metabolic surgery, specifically has been used effectively. Roux-en-Y gastric bypass reduces the size of the upper stomach and thus supports weight loss. In addition, it improves general metabolic problems like reduction of high blood sugar levels and amelioration of insulin sensitivity in muscles, liver and fat tissues.

Are there any side-effects to treatment?

Medical therapy is tailored to the individual who will be counselled on the benefits and potential side effects of any treatments recommended. 

What are the long-term implications of Lipodystrophy?

Lipodystrophy is a lifelong medical condition; the implications vary between patients and usually are related to the extent of adipose tissue loss.

  •  Metabolic: Short-term

The metabolic complications that are seen in those affected by lipodystrophy include diabetes, increased triglyceride levels and fatty liver disease.

  • Metabolic: Long-term

We know that these complications (diabetes and high triglycerides) are associated with an increased risk of heart disease and stroke and in the case of fatty liver disease there is a risk of liver scarring and cirrhosis. Preventing the development of these complications though early diagnosis of lipodystrophy or the early recognition of complications as they develop is important so that the correct treatment and follow-up can be implemented reducing the risk to the health of those affected.

  • Psychological

Lipodystrophy is not only a chronic condition that requires long-term medical follow-up but it is also an appearance altering condition.  Many people who are affected with lipodystrophy can experience psychological and emotional distress.

Where can I find more information and help?

The National Severe Insulin Resistance Service is a specialised NHS service for people with lipodystrophy and/or other forms of severe insulin resistance. The service is based at Addenbrookes Hospital in Cambridge.  You can contact the service directly or ask your GP or other specialist teams to refer you for consideration for an appointment.


Last reviewed: Oct 2019