Lipodystrophy can be caused by metabolic abnormalities due to genetic issues. These are often characterized by insulin resistance and are associated with metabolic syndrome.

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

AGL with autoimmune origin is responsible for about 25% of all AGL reports. Those with autoimmune origin stems from other autoimmune diseases, most commonly with juvenile dermatomyositis and autoimmune hepatitis, but also occurs with rheumatoid arthritis, systemic lupus erythematous, and Sjogren syndrome.

About 25% of previously reported AGL is associated with panniculitis. Panniculitis is an inflammatory nodules of the subcutaneous fat, and in this type of AGL, adipose destruction originates locally at the infection or inflammation site and develops into generalized lipodystrophy.

Lipodystrophy can be divided into the following types:

- Congenital lipodystrophies

- Congenital generalized lipodystrophy (Beradinelli-Seip syndrome)

- Familial partial lipodystrophy

- Marfanoid–progeroid–lipodystrophy syndrome

- Acquired lipodystrophy

- Acquired partial lipodystrophy (Barraquer-Simons syndrome)

- Acquired generalized lipodystrophy

- Centrifugal abdominal lipodystrophy (Lipodystrophia centrifugalis abdominalis infantilis)

- Lipoatrophia annularis (Ferreira-Marques lipoatrophia)

- Localized lipodystrophy

- HIV-associated lipodystrophy

A mutations in a number of genes have been associated with this condition. Mutations associated with FPL have been reported in "LMNA" (lamin A/C), "PPARG" (PPARγ), "AKT2" (AKT serine/threonine kinase 2), "PLIN1" (perilipin-1), and "CIDEC" (cell-death-inducing DFFA-like effector B).

Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion.

Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. Fat loss is confined to the limbs and mostly in the distal parts. Central obesity may be present. Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975.

Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the LMNA gene. Over 500 cases have been reported to date. Development up to puberty is normal. Fat is then gradually lost in is the limbs and trunk. Fat may accumulate around the face and between the shoulder blades. Insulin resistance is common. Other conditions associated with this condition include acanthosis nigricans, fatty liver, hypertriglyceridemia and polycystic ovary syndrome in women. There is an increased risk of coronary heart disease. Cardiomyopathy and muscular dystrophy may occur rarely. Xanthoma and nail changes may occur.

Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 but tends to be milder.

Type 4 is due to mutations in the PLIN1 gene. It is rare with only a small number of cases reported. Fat loss tends to affect the lower limbs and buttocks. Insulin resistance and hypertriglyceridemia occur. Calf muscular hypertrophy may occur.

Type 5 is due to mutations in the AKT2 gene. It has been reported in four patients all members of the same family. Fat loss affects the upper and lower limbs. The patients also suffered from hypertension, insulin resistance and hypertriglyceridemia.

Type 6 due to mutations in the CIDEC gene. It is inherited in an autosomal recessive fashion and has been reported in only one patient to date. Features included fat loss, severe insulin resistance, fatty liver, acanthosis nigricans and diabetes.

Congenital generalized lipodystrophy (also known as Berardinelli–Seip syndrome) is an extremely rare autosomal recessive skin condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.

There are differences in how Type 1 vs Type 2 patients are affected by the disease. In type 1 patients, they still have mechanical adipose tissue, but type 2 patients do not have any adipose tissue, including mechanical. In type 2 patients, there is a greater likelihood of psychomotor retardation and intellectual impairment.

Dunnigan-type familial partial lipodystrophy, also known as FPLD Type II and abbreviated as (FPLD2), is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. It can also result in hepatic steatosis. FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C.

The exact mechanism of HIV-associated lipodystrophy is not fully elucidated. There is evidence indicating both that it can be caused by anti-retroviral medications and that it can be caused by HIV infection in the absence of anti-retroviral medication.

On the other hand, there is evidence that HIV-1 infection on its own contributes to the development of the lipodystrophic phenotype by interfering with some key genes of adipocyte differentiation and mitochondrial function on patients which have not received antiretroviral treatment.

Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associated with Marfan syndrome, an appearance resembling that seen in neonatal progeroid syndrome (NPS; also known as Wiedemann–Rautenstrauch syndrome), and severe partial lipodystrophy. It is a genetic condition that is caused by mutations in the "FBN1" gene, which encodes profibrillin, and affects the cleavage products of profibrillin, fibrillin-1, a fibrous structural protein, and asprosin, a glucogenic protein hormone. As of 2016, fewer than 10 cases of the condition have been reported. Lizzie Velasquez and Abby Solomon have become known publicly through the media for having the condition.

In addition to severe lipodystrophy (loss of adipose tissue), individuals with MPL show a concomitant marked loss of lean tissue mass, which also contributes to their "skinny" appearance. Based on visual inspection, it was originally thought that the lipodystrophy associated with MPL was generalized. However, it appears in fact to be partial, being confined to the face, distal extremities, and the and lateral regions of the buttocks. Normal amounts of subcutaneous fat are found in the torso over the chest and abdomen. As such, the breasts are normal in females with MPL.

Individuals with MPL have an appearance of being prematurely aged, but this is not due to actual early aging and is instead due to their paucity of subcutaneous fat. As such, MPL is not truly a form of progeria.

In 2016, it was discovered that the partial lipodystrophy associated with MPL is caused by loss of the C-terminal domain cleavage product of profibrillin and novel glucogenic protein hormone, which has been named asprosin. Due to asprosin deficiency, individuals with MPL eat less, and do not gain weight or develop symptoms of diabetes like insulin resistance. MPL patients burn less energy than normal individuals, but also consume less, and their net energy balance is moderately reduced. In contrast to MPL patients, whose asprosin is undetectable in the blood, individuals with obesity and diabetes have elevated levels of asprosin. As such, "FBN1" has been nicknamed the "thin gene", and drug development for targeted inhibition of asprosin signaling is considered to be an "unusually promising" potential therapeutic route in the treatment of obesity and diabetes.

Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet. Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily due to a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.

The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of a pint (~568 ml) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors' findings, while others dispute them. A systematic review of four randomized controlled trials found that a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components.

Around 250 cases have been reported since the recognition of this syndrome. It is a rare syndrome with no known prevalence, although it is more common than the generalized form of acquired lipodystrophy (Lawrence syndrome).

- Race: No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent.

- Age: The median age of onset of lipodystrophy has been reported to be around seven years; however, onset occurring as late as the fourth or fifth decade of life also has been reported. The median age at presentation has been about 25 years, and women have been found to present later than men (age 28 for women, age 18 for men).

- Sex: Analysis of the pooled data revealed female patients were affected about four times more often than males.

Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndrome's prevalence is seen in most populations around the world.

Many people with MDP syndrome are high achievers intellectually following careers in law, medicine and computing. A crucial point is that they do not have progeria and there is no evidence of accelerated intellectual decline with age in these patients. Equally life expectancy has not been shown to be reduced. Patients of 65 have been described in the literature and none of the patients are known to have malignancy. Therefore, there are many crucial differences with progeria and the name of progeroid in the title is confusing as this really refers to the lack of fat in the face and taut skin and not any intellectual or other age associated features.

Estimating the mortality rate based on the available literature is difficult. Several case reports have revealed an association between acquired partial lipodystrophy and other diseases.

Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in about 20% of patients. Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years. Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria.

The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. This condition is responsible for most recurrent hospital admissions in patients with acquired partial lipodystrophy. Rapid progression of renal disease in a pregnant patient was reported. Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.

Associated autoimmune diseases (e.g., systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population. Although uncommon, insulin resistance increases cardiovascular risk. Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing.

Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes.

As fat cannot be stored under the skin it is important to have a healthy diet without excess fat. Often due to failure to thrive or lack of subcutaneous fat there may have been encouragement to add supplements or fat to the diet however this will not result in any increase in fat under the skin and can easily result in it going into tissues such as the liver or kidney where it is not desired. In people with moderate / severe lipodystrophy a low fat diet would be recommended but in those where the lipodystrophy has not progressed (for example in younger children) a healthy relatively low fat diet may be sufficient. The fat and muscle reduction is not the result of dietary insufficiency and cannot be treated with dietary measures. Apart from diet the other thing that is important is exercise which should be encouraged and will make insulin work more effectively.

In those who have not developed diabetes it is recommended fasting insulin, triglycerides, glucose and HbA1c should be measured annually to monitor insulin resistance and blood glucose.

In those with diabetes it is suggested using Metformin in doses of at least 2g/day as it decreases insulin resistance and improves insulin sensitivity, following appropriate clinical consultation.

The thin skin means if there is trauma there should be rapid attention to any wounds to avoid infection and help primary healing as there can be problems with skin ulcers.

In 2016 the United States Preventive Services Task Force concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.

Centrifugal abdominal lipodystrophy (also known as "Centrifugal lipodystrophy," "Lipodystrophia centrifugalis abdominalis infantalis") is a skin condition characterized by areas of subcutaneous fat loss that slowly enlarge.

Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment in order to stop the autoinflammatory response altogether. This suggests that the condition also involves IFN dysregulation.

Hypertriglyceridemia denotes high ("hyper-") blood levels ("-emia") of triglycerides, the most abundant fatty molecule in most organisms. Elevated levels of triglycerides are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels), and predispose to cardiovascular disease. Very high triglyceride levels also increase the risk of acute pancreatitis. Hypertriglyceridemia itself is usually symptomless, although high levels may be associated with skin lesions known as "xanthomas".

The diagnosis is made on blood tests, often performed as part of screening. Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders ("secondary hypertriglyceridemia") or whether no such underlying cause exists ("primary hypertriglyceridaemia"). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia.

Weight loss and dietary modification may improve hypertriglyceridemia. The decision to treat hypertriglyceridemia with medication depends on the levels and on the presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate class. Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main drug treatment for moderate hypertriglyceridemia where reduction of cardiovascular risk is required.

Primary lymphedema is a form of lymphedema which is not directly attributable to another medical condition.

It can be divided into three forms, depending upon age of onset: congenital lymphedema, lymphedema praecox, and lymphedema tarda.

Congenital lymphedema presents at birth. Lymphedema praecox presents from ages 1 to 35. This type of lymphedema accounts for 77–94% of all cases of primary lymphedema. Lymphedema tarda presents after age 35. This type of lymphedema usually develops as a result of a developmental abnormality being precipitated by some insult such as trauma, illness, or physical immobility. Compared to secondary lymphedema, primary lymphedema is more likely to involve the face, conjunctiva, and genitalia in association with any limbs involved.

It can be familial.

Lipoatrophia annularis (also known as "Ferreira–Marques lipoatrophia") is a skin condition affecting primarily women, characterized by the loss of subcutaneous fat in the upper extremity.

It is a form of lipodystrophy.