Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue.[1][2] The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy (from Greek lipo 'fat' and dystrophy 'abnormal or degenerative condition'), is used when describing the loss of fat from one area (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis. The absence of fat tissue is associated with insulin resistance, hypertriglyceridemia, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome.[3][4]
| Lipodystrophie | |
|---|---|
| Specialty | Endocrinology  |
Types
editLipodystrophy can be divided into the following types:[5]: 495–7
- Congenital lipodystrophy syndromes
- Acquired lipodystrophy syndromes
- 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
Pathogenesis
editDue to an insufficient capacity of subcutaneous tissue to store fat, fat is deposited in non-adipose tissue (lipotoxicity), leading to insulin resistance.[7] Patients may display hypertriglyceridemia, severe fatty liver disease and little or no adipose tissue.[8] Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death.[8] In contrast to the high levels seen in non-alcoholic fatty liver disease (NAFLD) associated with obesity, leptin levels are very low in lipodystrophy.[7]
Insulin injections
editLipodystrophy can appear as a lump or small dent in the skin that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with diabetes, using purified insulins and new needles with each injection may also help. (Although, in some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.)[citation needed]
Some of the side-effects of lipodystrophy are the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma which can cause bleeding that, in turn, causes rejection of the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the condition to worsen.[citation needed]
Antiretroviral drugs
editLipodystrophy can be a possible side effect of certain antiretroviral drugs. Lipoatrophy is most commonly seen in patients treated with thymidine analogues and other older HIV drug treatments such as the nucleoside reverse transcriptase inhibitors [NRTIs] [9] like zidovudine (AZT) and stavudine (d4T).[10] Other lipodystrophies manifest as lipid redistribution, with excess, or lack of, fat in various regions of the body. This is often most noticeable in the face. These include, but are not limited to, having sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump)[11] which also exhibits due to excess cortisol (a so-called "stress" hormone).
Diagnosis
editThe diagnosis is a clinical one, usually established by an experienced endocrinologist.Using a skinfold caliper to measure skinfold thickness in various parts of the body or a total body composition scan using Dual-energy X-ray Absorptiometry may also help identify the subtype.[4][12] Dual-energy X-ray Absorptiometry may be useful by providing both regional %fat measurements, and direct visualization of fat distribution by means of a "fat shadow".[13] A genetic confirmation is sometimes possible, depending on the subtype. However, in up to 40% of partial lipodystrophy patients, a causative gene has not been identified.[3]
Treatment
editLeptin replacement therapy with human recombinant leptin metreleptin has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by the FDA for the treatment of generalized lipodystrophy syndromes.[14] In Europe based on EMA, metreleptin should be used in addition to diet to treat lipodystrophy, where patients have loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. The medicine is used in: adults and children above the age of two years with generalised lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome) and in adults and children above the age of 12 years with partial lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.[15]
Volanesorsen is an Apo-CIII inhibitor[16][17] that is currently being investigated as a potential therapeutic to reduce levels of hypertriglycerides in Familial Partial Lipodystrophy patients in the BROADEN study.[18]
Epidemiology
editCongenital lipodystrophy (due to inherited genetic defect) is estimated to be extremely rare, possibly affecting only one per million persons.[7] Acquired lipodystrophy is much more common, especially affecting persons with HIV infection.[7]
See also
editReferences
edit- ^ Phan J, Reue K (January 2005). "Lipin, a lipodystrophy and obesity gene". Cell Metabolism. 1 (1): 73–83. doi:10.1016/j.cmet.2004.12.002. PMID 16054046.
- ^ "UCLA/VA Researchers discover fat gene". Archived from the original on 2018-10-06. Retrieved 2017-06-15.
- ^ a b Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, Mungai L, Oral EA, Patni N, Rother KI, von Schnurbein J, Sorkina E, Stanley T, Vigouroux C, Wabitsch M, Williams R, Yorifuji T (December 2016). "The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 101 (12): 4500–4511. doi:10.1210/jc.2016-2466. PMC 5155679. PMID 27710244.
- ^ a b Ajluni N, Meral R, Neidert AH, Brady GF, Buras E, McKenna B, DiPaola F, Chenevert TL, Horowitz JF, Buggs-Saxton C, Rupani AR, Thomas PE, Tayeh MK, Innis JW, Omary MB, Conjeevaram H, Oral EA (May 2017). "Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort". Clinical Endocrinology. 86 (5): 698–707. doi:10.1111/cen.13311. PMC 5395301. PMID 28199729.
- ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
- ^ Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, López-Robledillo JC, Dadban A, Requena L, Paller AS (March 2010). "Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome". Journal of the American Academy of Dermatology. 62 (3): 489–95. doi:10.1016/j.jaad.2009.04.046. PMID 20159315.
- ^ a b c d Polyzos SA, Perakakis N, Mantzoros CS (2019). "Fatty liver in lipodystrophy: A review with a focus on therapeutic perspectives of adiponectin and/or leptin replacement". Metabolism: Clinical and Experimental. 96: 66–82. doi:10.1016/j.metabol.2019.05.001. PMID 31071311. S2CID 195661123.
- ^ a b Bruder-Nascimento T, Kress TC, Belin de Chantemele EJ (2019). "Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function". F1000Research. 8: F1000 Faculty Rev-1756. doi:10.12688/f1000research.20150.1. PMC 6798323. PMID 31656583.
- ^ Carr A, Workman C, Smith DE, Hoy J, Hudson J, Doong N, Martin A, Amin J, Freund J, Law M, Cooper DA (July 2002). "Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial". JAMA. 288 (2): 207–15. doi:10.1001/jama.288.2.207. PMID 12095385.
- ^ John M, McKinnon EJ, James IR, Nolan DA, Herrmann SE, Moore CB, White AJ, Mallal SA (May 2003). "Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients". Journal of Acquired Immune Deficiency Syndromes. 33 (1): 29–33. doi:10.1097/00126334-200305010-00005. PMID 12792352. S2CID 22845453.
- ^ Physical and Biochemical Changes in HIV Disease Eric S. Daar, M.D. MedicineNet, Accessed 22 September 2007
- ^ Guillín-Amarelle C, Sánchez-Iglesias S, Castro-Pais A, Rodriguez-Cañete L, Ordóñez-Mayán L, Pazos M, González-Méndez B, Rodríguez-García S, Casanueva FF, Fernández-Marmiesse A, Araújo-Vilar D (November 2016). "Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome". Endocrine. 54 (2): 411–421. doi:10.1007/s12020-016-1002-x. PMID 27473102. S2CID 19689303.
- ^ Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akıncı B, Horowitz JF, Brown RJ, Oral EA (October 2018). ""Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers". Diabetes Care. 41 (10): 2255–2258. doi:10.2337/dc18-0978. PMC 6150431. PMID 30237235.
- ^ Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A (February 2002). "Leptin-replacement therapy for lipodystrophy". The New England Journal of Medicine. 346 (8): 570–8. doi:10.1056/NEJMoa012437. PMID 11856796.
- ^ "Myalepta | European Medicines Agency". www.ema.europa.eu. 17 September 2018. Retrieved 2019-01-08.
- ^ Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL (December 2014). "Targeting APOC3 in the familial chylomicronemia syndrome". The New England Journal of Medicine. 371 (23): 2200–6. doi:10.1056/NEJMoa1400284. PMID 25470695.
- ^ Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, Geary RS, Hughes SG, Viney NJ, Graham MJ, Crooke RM, Witztum JL, Brunzell JD, Kastelein JJ (July 2015). "Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia". The New England Journal of Medicine. 373 (5): 438–47. doi:10.1056/NEJMoa1400283. PMID 26222559. S2CID 205096489.
- ^ "The BROADEN Study: A Study of Volanesorsen (Formerly ISIS-APOCIIIRx) in Patients With Familial Partial Lipodystrophy - Full Text View - ClinicalTrials.gov". Retrieved 2018-03-31.