In partial lipodystrophy, the remaining fat tissue is sometimes redistributed so that there is an accumulation of fat tissue in some areas of the body and a loss in others.
Adipose tissue is an important organ because it stores energy or calories that we consume in our diet as fat. It’s also important to remember that excess sugar/carbohydrates will likewise be stored by the body as fat. Normally, when people lose or gain weight, this is as a result of changes in the amount of fat stored in normal fat cells. In lipodystrophy the capacity for adipose tissue to store excess calories is reduced as the fat cells themselves are abnormal or even absent, so the fat must find another location in the body to reside. This is most commonly liver and muscle and referred to as ectopic (or visceral) fat.
The changes in adipose tissue as a result of lipodystrophy result in changed physical appearance. In addition, ectopic fat may cause a number of metabolic complications, which have significant impact on the health of those affected. The amount of fat loss determines the severity of metabolic complications.
Different types of Lipodystrophy
There are many different sub-types of lipodystrophy, some of which are coded for in our DNA and termed inherited, familial or congenital, while others are acquired meaning there is no inherited component.
Based on the clinical findings and family history, some patients affected by lipodystrophy will have genetic testing. Understanding if the cause of lipodystrophy is inherited is important as other family members may be affected and screening may be offered.
Of the lipodystrophies that are currently known about there are two basic forms: total or generalised lipodystrophy, where all or almost all fat tissue is absent from birth; and partial lipodystrophy, where there is a partial loss of fat tissue that may not become apparent until after puberty.
Acquired Lipodystrophies
Acquired lipodystrophies appear not to be inherited and may have been triggered by various environmental factors. They may occur in conjunction with certain medications or autoimmune disease or after a viral infection. However, in certain cases, the cause of acquired lipodystrophy is unclear. Acquired lipodystrophy can develop at any stage of life and as with genetic causes it can result in a complete or partial reduction in adipose tissue.
Acquired Partial Lipodystrophy, APL (Barraquer-Simons Syndrome)
Characterised by a progressive change in appearance with loss of fat from the face, upper limbs and upper trunk. Usually, however, the lower limbs and lower part of the trunk are spared. As these people usually have quite a large amount of remaining fat, they often avoid the metabolic complications of lipodystrophy. This condition sometimes has associated kidney damage.
Acquired Generalised Lipodystrophy, AGL (Lawrence Syndrome)
Characterised by a near total absence of body fat and metabolic complications. Occasionally acquired partial lipodystrophy can progress to involve all body fat. These people develop all the metabolic problems seen in congenital generalised lipodystrophy.
HIV-associated Lipodystrophy
HIV infection and its treatment are the common cause of lipodystrophy worldwide. However, the metabolic problems associated with it tend to be relatively mild. This form of acquired lipodystrophy is estimated to affect more than 100,000 patients in the United States and many more in other countries. There are lots of charities available to help those affected by HIV, and LDUK works to support the rare suffers of lipodystrophy, which is not HIV-related.
Localised Lipodystrophy
Localised lipodystrophy can occur due to injection under the skin (subcutaneous) of various drugs, panniculitis (inflammation of subcutaneous adipose tissue), pressure, and other mechanisms. It presents with subcutaneous fat loss from a focal region resulting in a dimple or a crater with overlying skin usually unaffected. In some patients, large contiguous or anatomically distinct areas on any region of the body may be involved.
Inherited Lipodystrophies
To date, there have been over 20 different genes linked to various inherited lipodystrophies. Most of the genes implicated appear to be involved in the development and function of adipose tissue, and can result in both partial and generalised forms of lipodystrophy.
Congenital Generalised Lipodystrophy (CGL)
Characterised by a near total absence of body fat, generalised muscularity and metabolic complications. This is the more severe form of inherited lipodystrophy and involves loss of almost all body fat. The diagnosis of these types of lipodystrophy usually becomes apparent at birth or in the first few months of life, often because affected children look very muscular due to the absence of fat. As well as the different appearance of lipodystrophy, people suffering these conditions are at the severe end of the spectrum of metabolic problems that are associated with lipodystrophy. CGL is extremely rare and you have a low possibility of passing it on to your children.
Progeroid Syndromes
Characterised by a partial or generalised absence of body fat, progeroid features (such as large eyes, a thin, beaked nose, thin lips, small chin and jaw), and variable metabolic complications.
Familial Partial Lipodystrophy (FPLD)
Characterised by an absence of fat in the arms, legs and (sometimes) trunk although the face and neck are spared. Because of this, extra fat is often seen in the face and neck. Once again, problems include those relating to the lipodystrophic, muscular appearance of arms and legs and those caused by the metabolic complications of having reduced fat tissue. These metabolic complications are often less severe than in generalised lipodystrophy and can be rather variable between people with the same genetic alterations. Women tend to be more severely affected than men.
While still uncommon, FPLD is much less rare than generalised lipodystrophy and for most forms of FPLD there is a 50% chance of passing on the condition to your children. Several different genetic causes of this type of lipodystrophy are now known. The most common is Dunnigan type lipodystrophy or Dunnigan-Köbberling syndrome (FPLD2). Because the extent of fat loss is less widespread, these conditions are often more subtle, and commonly become apparent around the age of puberty. Furthermore, because women normally have more fat tissue then men, these conditions are much more commonly diagnosed at this time in women, although there is an equal likelihood of men and women being affected.
Auto-Inflammatory Lipodystrophy Syndrome
Characterised by a variable absence of fat with variable metabolic complications.
Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Reiger anomaly and teething delay (SHORT) Syndrome
Characterised by a variable loss of body fat and metabolic complications.
For more details about the various sub-types of inherited lipodystrophies, see the section: Inherited Lipodystrophies – Understanding the Genetics
Acquired Partial Lipodystrophy
Acquired Partial Lipodystrophy is not inherited, may often be attributed to follow a viral infection and is frequently associated with the presence of an antibody in the circulation that accelerates the “complement pathway”. This is a pathway normally required for the protection of the body against infection, but when abnormally activated may instead cause damage to the body itself.
How is Lipodystrophy Diagnosed?
Lipodystrophy is a diagnosis based on clinical assessment; in cases of generalised absence of adipose tissue it is important to exclude calorie (food) deprivation as the underlying cause. Additional blood tests may be carried out such as hormones produced by fat cells (adipokines). In cases where a genetic cause is suspected specific genetic tests may also be performed.
Key symptoms include lean or non-obese people with early diabetes, severe high blood levels of triglycerides (hypertriglyceridemia), accumulation of fat in the liver (hepatic steatosis), enlarged liver and spleen (hepatosplenomegaly), dark, velvety hyperpigmentation of the skin (acanthosis nigricans), and polycystic ovarian syndrome (affects a woman’s hormone levels).
What are the Signs and Symptoms of Lipodystrophy?
People affected with lipodystrophy are affected in a variety of ways.
- Altered Appearance: A key symptom and difficulty for those affected by lipodystrophy, is the change in appearance associated with the onset of symptoms.
- Reduced fat. The normal contours of the face and body are partly determined by fat tissue. When fat tissue is absent, reduced or abnormal in shape then alterations in appearance occur. The absence of fat under the skin can also be associated with the increased prominence of muscles and blood vessels. These alterations may be distressing, particularly in females who normally have a greater amount of fat under the skin. In certain forms of partial lipodystrophy there can be an increase in adipose tissue in certain parts of the body, typically the abdomen (tummy), face (double chin), neck (Cushingoid appearance: facial puffiness and weight gain), and between the shoulder blades (buffalo hump). Some women also experience increased adipose tissue in the labia.
- Enlargement of muscles (muscular hypertrophy) For reasons that are not well understood, people with lipodystrophy quite often have large muscles, especially in legs and arms, leading to an athletic appearance.
- Skin changes: Lipodystrophy is often associated with increased insulin production by the body. This can result in changes to the skin, which includes thickening, darkening and a velvet appearance in natural skin creases called acanthosis nigricans, which typically affects the neck, inside of the elbow, underarm and groin, although it can sometimes be more widespread. It is not a serious condition in its own right but can lead to further distress about appearance. In some people with lipodystrophy an increased number of skin tags are seen.
Metabolic Disturbance: Fat tissue is where we normally take any excess calories we consume and store this as a fatty substance called triglyceride. We depend on our triglyceride stores for our survival during periods of fasting. People who have more severe forms of lipodystrophy can develop a number of problems with their metabolism. They may find it difficult to fast for long periods, or to undertake prolonged exercise (although they may often be very good at shorter sprint-like activities).
- Severe, uncontrolled lipotrophic diabetes may be the first presentation of lipodystrophy. Patients are often severely insulin resistant and those who have to inject insulin to control their diabetes frequently have to inject very high doses. This is usually (mistakenly) characterised as type 2 diabetes.
- Leptin deficiency (hyperleptinemia) Fat cells make a hormone called leptin, which amongst other things, is important for regulating appetite. The loss of fat cells in lipodystrophy means the body is unable to produce the right amount of leptin. This means hunger signals are sent to the brain, even when it is not appropriate (for example, after eating). People with low leptin levels struggle to manage their appetite and often eat much more than is required, because their brain is getting the wrong signals and thinks they are hungry. This can be very dangerous as people affected are unable to store any excess calories consumed in healthy fat tissue, so it ends up in the wrong places, such as muscle, liver and pancreas. In these places it interferes with the normal action or production of insulin and diabetes often develops. Extreme hunger (hyperphagia) is often one of the symptoms that most troubles those affected and has a huge impact on their daily lives.
- High triglycerides (hypertriglycerideamia) Triglyceride levels also build up in the blood and if these reach high levels they can come out on the skin as a rash (eruptive xanthoma) or, more seriously, damage the pancreas (acute pancreatitis). Those affected may also have low levels of high-density lipoprotein (HDL) cholesterol – the ‘good’ cholesterol.
- Acute pancreatitis is a serious condition where the pancreas becomes inflamed over a short period of time. Your pancreas processes most of the fat you eat. So, the more you eat, the harder your pancreas works. High-fat foods and simple sugars increase your triglyceride levels, which boosts the amount of fat in your blood. In lipodystrophy, because fat can’t be stored properly, those affected are more at risk from pancreatitis.
- Organ damage Excess fat in the blood can get stored around various organs, which can impair their function.
- Fatty liver or non-alcoholic fatty liver disease (NAFLD) is an example of organ damage that is very common in people with lipodystrophy. In some cases, long standing excessive storage of fat in the liver can lead to inflammation in the liver (hepatitis)and sometimes even to irreversible liver scarring (cirrhosis).
- Cardiovascular disease Because patients with lipodystrophy often have diabetes and high levels of fat in their blood stream they often suffer from high blood pressure and are more at risk of heart attacks and strokes. Much of the treatment given in lipodystrophy aims to reduce the long-term chances of these problems as much as possible, although at the time of treatment symptoms are often not apparent.
- Sex hormones and fertility High insulin levels in the blood result when the pancreas tries to overcome insulin resistance by making more insulin. High insulin levels change the balance of male and female hormones produced by the ovary. The main problems that result are irregular periods, sometimes associated with extra hair growth (hirsutism) in a male-type distribution and development or worsening of acne. The actions of high levels of insulin on the ovaries sometimes impair ovulation, which can lead to problems with fertility. This combination of problems is very similar to that seen in polycystic ovary syndrome, which to some degree may affect up to 5% of women of reproductive age. There is no evidence that lipodystrophy affects sex hormones or fertility in men.
Additional Complications: As well as the metabolic disturbances associated with lipodystrophy, there may be other complications that those affected sometime experience. People with lipodystrophy often report reduced quality of life with increased overall pain (requiring frequent use of pain medications), sleep disturbances and sleep apnea, muscles of the digestive system not working as they should (gastrointestinal dysmotility), mood disturbances such as depression and anxiety and psychiatric diseases.
- Muscle pain/tension/tear High levels of intermuscular adipose tissue are associated with insulin resistance, a loss of strength, and mobility dysfunction. In addition, tension in the increased muscle mass is quite common and can lead to additional complications such as pain and muscular tearing.
- Carpal tunnel is reported by the community and may sometimes be linked to (diabetic) neuropathy. It is a condition that causes numbness, tingling, or weakness in your hand. It happens because of pressure on your median nerve, which runs the length of your arm, goes through a passage in your wrist called the carpal tunnel, and ends in your hand.
- Fatigue Affected individuals may also experience fatigue, which is sometimes associated with high insulin levels. This can make every day activities difficult. Fatigue is also common in depression, in which case, treatment of depression may alleviate fatigue.
- Body Image Lipodystrophy can contribute to negative body image affecting the daily lives of people with lipodystrophy. Those affected would benefit from psychological support alongside medical management. LDUK is working with the National Service for Treatment of Lipodystrophy in Addenbrooke’s Hospital, Cambridge, UK, to ensure appropriate support is made available.
- Mental Health As well as body confidence, it is common for people to struggle come to terms with the diagnosis of a rare disease, and with the day-to-day management of their condition. It is important to take steps to maintain your mental wellbeing, and to surround yourself with supportive people. It can help if you ‘take ownership’ of your lipodystrophy – do what you can to keep yourself healthy with a good diet and exercise, and don’t ever be ashamed of who you are or of your lipodystrophy diagnosis. #TogetherWeAreStrong
How is Lipodystrophy treated?
There is currently no cure for lipodystrophy and there is no specific treatment that will increase adipose tissue. However, there are lots of things that can be done to reduce the impact of the condition. The main treatment focus in lipodystrophy is a low fat diet. The aim of dietary therapy is to reduce the amount of ectopic fat in organs such as the liver, which will contribute to insulin resistance and the complications of lipodystrophy. More work is also being done to investigate the impact of a low carb diet in people with lipodystrophy. A low carb diet has been shown to dramatically improve the health of people with type 2 diabetes. Anecdotally, similar health benefits have also been seen in the lipodystrophy community. For those of us with lipodystrophy, the key is to ensure low carbohydrate intake while still maintaining a low fat intake. Some early adopters of this diet have reported improved insulin sensitivity (and reduced insulin requirements), as well as increased energy levels. More research needs to be done to understand the affect of this diet in people with lipodystrophy, but early indications are promising.
Physical activity is also really important. Exercise can help to improve insulin sensitivity, reduce triglycerides and reduce/prevent the build up of excess fat around your organs. The combination of a low fat (possibly low carb), healthy balanced diet with regular physical activity is the best thing you can do to help your body stay healthy. Other benefits to regular physical activity include improved heart health, improved mood and increased energy levels. You don’t have to hit the gym for two hours every day to feel the benefit; take the stairs instead of the lift, get off the bus a stop early, swift walking and housework all count towards increasing your physical activity!
In certain types of lipodystrophy, metreleptin therapy is often used. Leptin is a hormone, which is made by adipocytes (fat cells). 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 and have a negative effect on metabolism. In such cases metreleptin therapy can be used as a treatment, which reduces appetite and improves some of the metabolic complications of the condition. Metreleptin is most effective in people with total lipodystrophy where it improves diabetes control, hypertriglyceridaemia, and fatty liver. It has also been shown to be of some benefit in people with partial lipodystrophy and low leptin levels.
Where specific complications arise such as diabetes and dyslipidaemia, medication specific to those conditions may be used. It is not uncommon for lipodystrophy patients with diabetes to require high doses of insulin (because of insulin resistance), in that instance concentrated forms of insulin therapy or sometimes insulin pump therapy may be needed. Among patients with partial lipodystrophy and metabolic complications that are not adequately controlled using conventional therapy, metabolic surgery, specifically Roux-en-Y gastric bypass had been used effectively.
Because reversal of the lost adipose tissue is not possible, cosmetic surgery is sometimes used. Unwanted excess adipose tissue can be surgically excised or removed by liposuction. Those with severe facial lipodystrophy can undergo reconstructive facial surgery including fascial grafts and insertion of fillers. Some women also undergo breast augmentation. However, while excess fat can be removed, the body commonly re-accumulates fat in the same areas. In addition, fillers can move position and slip, possibly because the lack of fat under the skin means the filler is not held in place.
Are there any side effects to treatment?
Therapy is tailored to the individual and your prescribing clinician should explain the benefits and risks of each treatment option. However, side effects related to diabetic medication are possible if these medications are required.
Important note: Thiazolidenediones such as pioglitazone, commonly used in the treatment of diabetes, should be used with caution in people with lipodystrophy as they could theoretically cause fat expansion in the remaining fat in patients with partial lipodystrophy and may worsen fatty liver in patients with total lipodystrophy. If you are unsure, speak to your clinician.
How Common is Lipodystrophy?
Lipodystrophy is considered to be an ultra-rare disease. Worldwide the estimated prevalence of diagnosed lipodystrophy is 3.07 cases/million¹. This is made up of generalised lipodystrophy at 0.23 cases/million and partial lipodystrophy at 2.84 cases/million. However, this is probably an underestimate, with most undiagnosed cases likely being for partial lipodystrophy. Partial lipodystrophy is most frequently diagnosed in females; however, it is unlikely that this is because lipodystrophy affects more females than males but because fat loss is often easier to recognise in females.
Dr Sam Rice, Leanne Jenkins and the Diabetes Network Wales saw the need, found the funds and collaborated with colleagues in Addenbrookes Cambridge and Lipodystrophy UK to make the videos shown on this page. They, in turn, worked with the team at eHealth Digital Media to make these films which can also be found in the PocketMedic film library https://pocketmedic.org/ where you can find information about self-management of a range of conditions.
¹Chiquette E, Oral EA, Garg A, Araújo-Vilar D, Dhankhar P. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes Metab Syndr Obes. 2017;10:375–383. Published 2017 Sep 13. doi:10.2147/DMSO.S130810
