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TREATMENT OF LIPODISTROPHY

Prof. David Araújo-Vilar

 Current treatments prevent or improve the comorbidities of lipodystrophies. However there is no cure for lipodystrophy, and there is no treatment that can regenerate adipose tissue.

DIET

1.Most patients should follow diets with a balanced composition of macronutrients.

2.Low-calorie diets improve metabolic disorders and may be appropriate in adults.

3.Diets with very low fat content should be used in acute pancreatitis induced by hyper Chylomicronemia.

4.You should consult an endocrinologist for ticas and specialized diet needs, especially beb é s Kids ñ os os smallOverfeeding should be avoided.

5.Oily formulas triglic é glycerides of medium chain (MCT) can provide energy and reduce triglic é glycerides in beb é s.

The cornerstone of therapy for metabolic complications of lipodystrophy is diet. Studies of specific diets in lipodystrophy are insufficient, and these recommendations are based on scarce literature and clinical experience.

Patients with lipodystrophy, especially in generalized forms, are you ágicos HiPerf picamente due to leptin deficiency. Isocaloric diets reduce adolescents and adults ridos é triglic and glucose, but RESTRICTIO n THICS diet is a difficult challenge to achieve. ON caloric restriction to control metabolic complications it must be balanced with the requirements of growth in children. Overfeeding to achieve normal weight can worsen metabolic complications andsteatosis hepa tica (fatty liver). The evaluation of weight-for-height and body mass index (BMI) compared to the reference growth data is not adequate because the body composition is atypical . A low weight for length or BMI is acceptable as long as linear growth is maintained.

Patients must follow a diet with 50% -60% carbohydrates, 20% -30% fat and 20% protein. Simple sugars should be restricted, being preferred complex carbohydrates with high fiber content, distributed evenly between meals and snacks and consumed combinatio n with prote í nas or fats. The fat diet THICS I deberí to be mainly in the form of monounsaturated fats in cis and long chain omega-3 fatty acids. NIN riglicerid you extremely hyper t é monkeys,MCT based formulas may be helpful.

EXERCISE

1. Patients with lipodystrophy should be encouraged to exercise, as long as they do not exist specific contraindications.

2. Patients with lipodystrophy subtypes predisposed to cardiomyopathy (LMNA mutations, PTRF, BSCL2) should undergo cardiac evaluation before starting an exercise regime r é.

People with lipodystrophy who perform intense exercise usually get an improvement in their metabolic complications. Most patients should be encouraged to be physically active. However, strenuous exercise should be avoided in patients with myocardiopathy. They should also avoid contact sports patients with severe hepatosplenomegaly and patients with Berardinelli-Seip syndrome in which lesions have been found or be li tics.

METRELEPTIN (recombinant human leptin)

1.In generalized lipodystrophy, metreleptin (with diet) is a first-line treatment for metabolic and endocrine disorders, and can be considered for the prevention of these comorbidities in children.

2.The metreleptin could be indicated in patients hipoleptiné monkeys (leptin <4 ng / mL ) with partial lipodystrophy and severe metabolic disorders (HbA1c > 8% and / or triglic é ridos > 500 mg / dL ).

Currently, metreleptin (methionyl- leptin recombinant human) is the only medication approved specifically for lipodystrophy. It is approved in the USA as a supplement to the diet for the treatment of metabolic complications in patients with generalized lipodystrophy. In Japan, it is approved for both generalized and partial lipodystrophy. It is also available in other parts of the world (eg Europe) é s ACROSS compassionate use programs. There is no age limit for the start of metreleptin ; children as young as six months have been treated effectively. Dose adjustments should be made in response to metab ólicos pará meters and weight change with a EVALUATIO n cl INICA and laboratory performed every 3-6 months.

Side effects of metreleptin: Approximately 30% of patients experience side effects. Important má s cl ínicamente are hypoglycemia (in patients receiving concomitant insulin) and site reactions of inyecció n (erythema, urticaria),which are uncommon.

The activity of neutralizing antibodies in vivo for leptin has been reported. The clinical implications remain unclear, but may include failure of treatment and sepsis Adverse events Additional serious conditions that occur during treatment with metreleptin are probably related to the type of underlying lipodystrophy, rather than to the drug. These include lymphoma c é T cells in patients with acquired generalized lipodystrophy, pancreatitis acute and worsening of liver and kidney disease.

Additional treatments for comorbidities specific ficas

DIABETES

1.Metformin is a first - line agent for diabetes and insulin resistance.

2.Insulin is effective for hyperglycemia. In some patients, concentrated preparations and high doses may be required.

3.Thiazolidinediones may improve metabolic complications in partial lipodystrophy, but should be used with caution in generalized lipodystrophy.

Among oral hypoglycaemic agents, metformin is used more frequently. In patients with partial lipodystrophy, thiazolidinediones improved HbA1c, the triglic é ridos, hepatic steatosis volume, but may increase the regional excess fat.In patients with high insulin requirements, concentrated insulins should be considered. The The pharmacokinetics of insulin glargine and insulin degludec can be altered when injected into areas lipo atrophic since its prolonged action requires subcutaneous fat. Patients with generalized lipodystrophy may need insulin saw intramuscular (IM) for lack of fat subcut cattail. They have used many others and lipid - hipogluc agents in lipodystrophy, but its effectiveness has not been studied in depth.

DISLIPIDEMIA

1.Statins should be used concomitantly with lifestyle modification (s é after considering age, reproductive status and tolerance).

2.Fibrates and / or omega-3 long chain fatty acids should be used for triglic é ridos > 500 mg / dl, and they can be considered for triglic é ridos > 200 mg / dL.

Lipids should be handled in accordance with US and European guidelines for the general population, with statins being first-line therapy. Statins and fibrates should be used with caution due to the increased risk of myopathy, especially in the presence of known myositis , or muscular dystrophy. Because the cardiovascular risk may increase in the lipodystrophy syndromes independent of other risk factors, the m é physicians may consider applying Lipí objectivesPhysicians m ore stringent (eg, LDL-cholesterol <100 mg / dl cholesterol , non - HDL <130 mg / dL, triglic é ridos <200 mg / dL ) in patients without diabetes. In addition to diet, fibrates and long-chain omega-3 fatty acids have a wide clinical use to avoid the acute complications of severe hypertriglyceridemia, but they have not been formally studied. The plasmaf é resis has been used in extreme hypertriglyceridemia, but must be repeated frequently. Noadditional lipid-lowering drugs have been studied in patients with lipodystrophy, although a phase II-III clinical trial is underway for hypertriglyceridemia in familial partial lipodystrophy.

ARTERIAL HYPERTENSION

1.Inhibitors of the converting enzyme from the Angiotensin ( ACE) or angiotensin receptor blockers (ARBs) are first-line treatments for hypertension in patients with diabetes.

HEPATOPATHY

Colic acid did not reduce hepatic steatosis in patients with familial partial lipodystrophy in a double-blind, placebo-controlled crossover study. In nonalcoholic steatohepatitis (NASH) not associated with lipodystrophy, diet and exercise are the first-line treatments, and among pharmacological treatments , Vitamin E (in children and adults) and pioglitazone (in adults) have shown the most consistent benefit for liver histopathology. However, these treatments have not been studied in patients with lipodystrophy and are not approved for NASH.

COSMETIC TREATMENT

1.Patients with lipodystrophy could be evaluated for anguish and anxiety related to lipodystrophy, and be derivatives to mental health professionals and / or plastic surgeons.

Changes in the physical appearance of lipodystrophy can cause anxiety and discomfort Fí SICO (p. E .., for the absence of fat pads on the feet or buttocks). Data regarding surgery is THICS are limited. For facial lipoescultura transferautologous fat can be used (in the acquired partial lipodystrophy) fillers or d é rmicos artificial Excess fat on the face, neck or vulva can be surgically reduced or lightened by liposuction. Breast implants could be advised in some women. Acanthosis nigricans is improved by the successful treatment of insulin resistance.

Contraception, hormone replacement therapy and pregnancy

1.Oral estrogens are contraindicated.

2.If contraception is needed, progestin- based contraceptives should be considered or not hormonal.

3.If estrogen replacement is needed, it should be use TRANSD estrogen rmico é s.

4.Pregnant patients should receive prenatal care from an obstetrician with expertise in managing diabetes and m é a physician experienced in the management of lipodystrophy.

5.If a patient becomes pregnant while taking metreleptin the m é physicians may consider continuing medication if abstinence could be harmful to the mother and fetus, and the patient understands that the effects of metreleptin in pregnancy are unknown (Category C from the FDA) and want to continue.

Oral estrogens are contraindicated in lipodystrophies due to the risk of severe hypertriglyceridemia and acute pancreatitis. The estrus genos TRANSD é rmicos may be safer because of reduced hepatic exposure. There is clinical experience in the safe use of oral progestogens and intrauterine devices that contain progestin.

In congenital forms, adequate genetic counseling should be provided by specialized physicians, assessing the possibility of screening the carrier status in case of pregnancy or pre-implantation diagnosis.

In patients with lipodystrophy with extreme insulin resistance, the worsening of insulin resistance during pregnancy can make it difficult to control diabetes with consequent fetal risks. In addition, the withdrawal of metreleptin has been associated with rebound hypertriglyceridemia , which puts patients at risk of pancreatitis, endangering both the mother and the fetus.

SURGERY

Bariatric surgery (surgery to reduce weight in obesity) may be indicated for the control of comorbidities in patients with partial family lipodystrophy, although the number of studies is limited.

(*): Translated and modified from: RJ Brown, D Araújo-Vilar, PT Cheung, D Dunger, A Garg, M Jack, L Mungai, EA Oral, N Patni, K Rother, J von Schnurbein, E Sorkina, T Stanley, C Vigouroux, M Wabitsch, R Williams, T Yorifuji. The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline. J Clin Endocrinol Metab 2016 Dec;101(12):4500-4511.

This guide It has the backing of the following societies scientific : 1. Pediatric Endocrine Society, 2. American Diabetes Association, 3. American Association of Clinical Endocrinologists, 4. Endocrine Society, 5. Japanese Society for Pediatric Endocrinology, 6. Australasian Pediatric Endocrine Group, 7. European Society for Pediatric Endocrinology, 8. Asia Pacific Pediatric Endocrine Society, 9. African Society for Pediatric and Adolescent Endocrinology, 10.International Society for Pediatric and Adolescent Diabetes.