What is Lipodystrophies?

Lipodystrophies are a group of conditions that all involve a reduction in body fat beneath the skin. There are many types of lipodystrophy, and they can either come from birth (congenital) or develop later in life (acquired). These different types can also vary in how fat loss is distributed throughout the body. Although all forms of lipodystrophy are quite rare, the acquired forms are becoming more frequent due to certain medications and medical interventions.

Regardless of the specific type, a reduction in overall body fat can lead to metabolic complications, which can increase the disease rate and death rate among people with lipodystrophy.

Congenital Generalized Lipodystrophy, also known as Berardinelli-Seip syndrome, is a rare form of lipodystrophy where there is significant, and sometimes nearly total, loss of fat.

Familial Partial Lipodystrophy is often a condition that is passed down in families where the fat loss mainly involves the limbs and more often the legs than the arms.

Acquired Generalized Lipodystrophy is an extremely rare condition where there is widespread fat loss under the skin.

Acquired Partial Lipodystrophy, or Barraquer-Simons syndrome, is characterized by the slow reduction of fat from the upper body and middle part of the body during childhood.

In the past couple of decades, lipodystrophy caused by highly active anti-retroviral therapy has become the most common form of Acquired Partial Lipodystrophy.

What Causes Lipodystrophies?

Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is a rare condition where a person loses a large amount of body fat. This condition is usually noticed at birth or in early infancy, and is caused by changes in certain genes, specifically AGPAT2, seipin, caveolin-1, and cavin-1.

Familial partial lipodystrophy is generally a condition that affects the fat in just the limbs, more commonly the lower than upper body. This condition is usually passed down in families and has a number of different types, caused by various gene mutations. One well-known type is Dunnigan’s lipodystrophy, which results from defects in the genes that produce proteins called lamins A and C.

Acquired generalized lipodystrophy is a very rare condition where a person gradually loses body fat. The cause of this condition is not well understood, but it may be linked to autoimmune connective tissue diseases, where the body’s immune system mistakenly attacks healthy tissues.

Acquired partial lipodystrophy, or Barraquer-Simons syndrome, is a condition in which fat is lost from the upper body and torso during childhood. While the cause of this condition is not confirmed, some studies suggest it might be linked to a reaction by the immune system that destroys fat cells. Recent years have seen an increase in this condition due to anti-retroviral therapy, a medication used to treat HIV, which is known to damage fat cells although the exact process remains unclear.

Lipodystrophy can also occur with the use of insulin injections, a treatment for diabetes. Patients may experience either a buildup of fat at the injection site (lipohypertrophy) or a loss of fat (lipoatrophy). Lipoatrophy often appears as a large scar on the skin, while lipohypertrophy results in a thick, rubbery swelling. Lipodystrophy can lead to inconsistent blood sugar levels and unexpected low blood sugar episodes, which can increase health care costs and negatively affect patient treatment adherence. Evidence shows that rotating the injection site can help prevent lipohypertrophy from developing.

Risk Factors and Frequency for Lipodystrophies

Congenital generalized lipodystrophy is an extremely rare condition with around 250 cases reported so far. There might be more unreported cases with estimates suggesting the rate could range from 1 in 200,000 to 1 in 12 million people. This condition usually starts showing signs from birth or early infancy.
Familial partial lipodystrophies have variants like Dunnigan’s lipodystrophy and Kobberling lipodystrophy. These are quite uncommon, with the Dunnigan’s variant thought to occur in less than 1 in 15 million people. It is typically passed down in families (autosomal dominant). Still, the Kobblering variant’s prevalence and transmission are less clear, though there have been a few cases.
Acquired generalized lipodystrophy is a condition documented in at least 100 patients, but it’s likely there have been more unreported cases. This condition generally starts showing up in adolescence. People with this condition might already have an existing condition, such as panniculitis, autoimmune issues, or an idiopathic condition; or the lipodystrophy could develop on its own. This condition affects women about three times as much as men.
Acquired partial lipodystrophy is another rare condition, with around 250 cases reported. Usually, it starts showing signs after puberty, with an average age of 25 at diagnosis. People from all ethnic backgrounds can have this condition, but most reported cases involve patients of European descent. Women are significantly more likely to have this condition than men, at ratios of between 4:1 and 8:1.

Signs and Symptoms of Lipodystrophies

Congenital Generalized Lipodystrophy is a condition where fat loss is widespread and results in a distinctive look. Patients experience not only a loss of fat but also an increase in muscle size due to the excess deposition of fat within the muscles. Other effects include higher levels of insulin, insulin resistance, and high levels of triglycerides in the blood, often seen before adulthood. This disease reduces the life expectancy due to complications linked to diabetes, or liver or heart disease.

Familial Partial Lipodystrophy is a condition that causes fat loss primarily in the limbs. Patients look normal from birth through childhood regarding fat distribution, but they start to show noticeable changes around puberty. While patients lose fat in their limbs, they gain fat in their face, neck, and abdomen. These patients also likely experience severe high levels of triglycerides, insulin resistance, heart issues, and fatty deposits in the liver.

Acquired Generalized Lipodystrophy is a condition characterised by normal fat distribution at birth, followed by gradual fat loss as time goes on. This mainly affects the face, arms, and legs. The absence of mature fat cells hampers the body’s ability to produce key substances important for metabolism, leading to severe metabolic issues. Fat deposition may occur in the liver, leading to scarring. People with this condition often have diabetes and high levels of triglycerides. Around a quarter of the patients develop inflammatory condition of the fatty tissue when fat loss starts.

Acquired Partial Lipodystrophy manifests as a gradual loss of fat from the upper body and trunk during childhood. As the condition progresses, patients may notice an increase in fat deposits in the hips and legs. Metabolic complications seen in other types of lipodystrophy aren’t as common in people with this condition. However, they may be more prone to kidney disease. Most patients have circulating levels of a certain immune system substance.

Highly active antiretroviral therapy-induced lipodystrophy is currently the most common form of Acquired Partial Lipodystrophy. It leads to loss of fat in the limbs and face, and fat gain in the trunk. Due to this unique presentation, it’s often associated with HIV.

In the case of Lipodystrophy Associated With Insulin Treatment, it is important for people taking insulin to seek detailed physical examinations. It’s not enough just to look; affected areas should be physically examined to check for abnormal growth of fat tissue.

Testing for Lipodystrophies

If your doctor suspects you might have lipodystrophy, a condition that affects the way your body stores fat, they’ll need to conduct some tests to confirm the diagnosis. Generally, these tests focus on revealing any problems in your metabolism – the complex set of chemical reactions that takes place in your body cells.

The first thing your doctor will likely do is request a complete metabolic test. This type of testing will check your blood for high sugar levels (hyperglycemia) and any changes in liver enzymes, which could show your liver isn’t functioning properly.

You may also need to have a cholesterol test. This test measures different types of fats in your blood, and it will be particularly important to rule out the presence of high levels of triglycerides (a type of fat) in your blood (hypertriglyceridemia).

Another test that can be useful checks the levels of leptin in your blood. Leptin is a hormone—essentially a chemical messenger—that plays a key role in regulating your body’s energy, including how many calories you eat and burn, as well as how much fat you have stored. If your leptin levels are low, it might mean you will respond well to treatment aimed at returning these levels to normal.

In certain types of lipodystrophy, your doctor might recommend genetic testing to confirm the diagnosis, but this isn’t routine at the moment. This type of testing can be done in a clinical laboratory and involves checking your DNA for specific genetic variants that are known to be associated with lipodystrophy.

Finally, it’s worth noting that there are ongoing clinical trials for various treatments for lipodystrophy. You can review them on the website www.clinicaltrials.gov. These trials might offer the chance to access new, experimental treatments.

Treatment Options for Lipodystrophies

The treatment of lipodystrophies, or abnormal body fat distribution, depends on the type and severity of the condition. For patients with serious metabolic disturbances, it’s necessary to use drugs that lower fat levels in the blood and manage diabetes. Research has shown that a drug called pioglitazone, intended to improve how the body uses insulin, seems more effective than metformin, another diabetes medication, for people with lipodystrophy. In severe instances, insulin itself may need to be used.

A type of medication called metreleptin, which functions similarly to a hormone called leptin, has proved effective in maintaining normal metabolism in patients who can’t effectively produce leptin naturally. Metreleptin is a man-made version of human leptin, and it’s the only such treatment currently approved by the FDA for certain patients with lipodystrophy.

In some cases, a drug called troglitazone may be used to deal with high levels of triglycerides (a type of fat) in the blood, but it might not successfully regulate all fat-related disorders in these patients. Moreover, for patients who have lipodystrophy that affects their physical appearance, there are treatments such as poly-L lactic acid and calcium hydroxyapatite, which are types of fillers that can help improve the look of the affected areas.

Further research is necessary in the field of lipodystrophies in order to establish clear diagnostic and treatment guidelines. As our knowledge of metabolic regulation improves, it’s likely that additional treatment options for people with these conditions will become available in the future.

Here are some medical conditions that need to be considered:

Tumour in the anterior hypothalamus
Centrifugal lipodystrophy, a rare fat loss disease
Skin symptoms of lipodystrophy
Fascial hemiatrophy, where half of the face significantly decreases in size
Generalized lipodystrophies, a fat loss condition affecting the whole body
Genetic factors linked to Cockayne syndrome, a rare genetic disorder
Lipodystrophy related to HIV
Other types of partial lipodystrophies, where fat loss is limited to certain parts of the body
Conditions with symptoms like body shortness, extremely stretchable joints, and hernia
Werner syndrome, a disorder that causes the body to age more quickly than normal

What to expect with Lipodystrophies

Acquired partial lipodystrophy is a condition where parts of the body lose their fat tissue. Research from Misra and colleagues found that how this condition affects a person’s health is largely dependent on whether they have kidney dysfunction. Notably, patients with acquired partial lipodystrophy who also have a kidney condition called membranoproliferative glomerulonephritis (MPGN) tend to develop lipodystrophy at an earlier age. On average, patients developed MPGN about 8 years from the diagnosis although the course of the disease can vary. Reports indicate that as many as 22% of patients with acquired partial lipodystrophy may develop MPGN.

Acquired generalized dystrophy is another type of lipodystrophy which affects the whole body. It is often associated with panniculitis, a condition that involves inflammation of the fatty layer of the skin, but is usually less severe than other forms of the lipodystrophy. When this form of lipodystrophy is linked to autoimmune diseases, patients tend to be more prone to other autoimmune diseases.

Lipodystrophy, in general, can cause serious health complications. It can be linked with hard-to-manage type 2 diabetes that might need high doses of insulin. Moreover, uncontrolled high levels of fats in the blood, also known as hypertriglyceridemia, could lead to repeated bouts of pancreatitis, an inflammation of the pancreas. The accumulation of fat in the liver may also result in liver scarring, known as cirrhosis.

Unfortunately, the loss of fat tissue in patients with acquired lipodystrophy is irretrievable, and patients might need cosmetic procedures to manage the physical aspects of the condition.

Preventing Lipodystrophies

Lipodystrophy, a disorder related to the way the body stores and uses fat, can be a side effect of insulin treatment and it can lead to inconsistent blood sugar levels. Sometimes, this might even cause hypoglycemia – a condition where your blood sugar drops below normal levels without any apparent reason. To avoid this, patients are recommended to change the sites of their insulin injections regularly and not to inject in any areas on their body affected by lipodystrophy. Also, patients should try not to repeatedly use the same insulin needle.

People with lipodystrophy have a higher risk of developing metabolic syndrome, a cluster of conditions like high blood pressure, high blood sugar, and abnormal cholesterol levels that collectively increase the risk of developing heart diseases. Because of this, it’s essential that folks with lipodystrophy receive timely medical treatment and take significant steps to improve their lifestyle for better health outcomes.