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Endocrinology and Metabolism Clinics of... Dec 2016Lipodystrophies are heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications.... (Review)
Review
Lipodystrophies are heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications. They are subclassified depending on degree of fat loss and whether the disorder is genetic or acquired. The two most common genetic varieties include congenital generalized lipodystrophy and familial partial lipodystrophy; the two most common acquired varieties include acquired generalized lipodystrophy and acquired partial lipodystrophy. Highly active antiretroviral therapy-induced lipodystrophy in patients infected with human immunodeficiency virus and drug-induced localized lipodystrophy are common subtypes. The metabolic abnormalities associated with lipodystrophy include insulin resistance, hypertriglyceridemia, and hepatic steatosis. Management focuses on preventing and treating metabolic complications.
Topics: Fatty Liver; HIV Infections; Humans; Hypertriglyceridemia; Insulin Resistance; Lipodystrophy; Syndrome
PubMed: 27823605
DOI: 10.1016/j.ecl.2016.06.012 -
The Journal of Clinical Endocrinology... Dec 2016Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes,... (Review)
Review
OBJECTIVE
Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs.
PARTICIPANTS
Seventeen participants were nominated by worldwide endocrine societies or selected by the committee as content experts. Funding was via an unrestricted educational grant from Astra Zeneca to the Pediatric Endocrine Society. Meetings were not open to the general public.
EVIDENCE
A literature review was conducted by the committee. Recommendations of the committee were graded using the system of the American Heart Association. Expert opinion was used when published data were unavailable or scarce.
CONSENSUS PROCESS
The guideline was drafted by committee members and reviewed, revised, and approved by the entire committee during group meetings. Contributing societies reviewed the document and provided approval.
CONCLUSIONS
Lipodystrophy syndromes are heterogeneous and are diagnosed by clinical phenotype, supplemented by genetic testing in certain forms. Patients with most lipodystrophy syndromes should be screened for diabetes, dyslipidemia, and liver, kidney, and heart disease annually. Diet is essential for the management of metabolic complications of lipodystrophy. Metreleptin therapy is effective for metabolic complications in hypoleptinemic patients with generalized lipodystrophy and selected patients with partial lipodystrophy. Other treatments not specific for lipodystrophy may be helpful as well (eg, metformin for diabetes, and statins or fibrates for hyperlipidemia). Oral estrogens are contraindicated.
Topics: Humans; Lipodystrophy; Practice Guidelines as Topic
PubMed: 27710244
DOI: 10.1210/jc.2016-2466 -
Journal of Endocrinological... Jan 2019Lipodystrophy syndromes are rare heterogeneous disorders characterized by deficiency of adipose tissue, usually a decrease in leptin levels and, frequently, severe... (Review)
Review
AIM
Lipodystrophy syndromes are rare heterogeneous disorders characterized by deficiency of adipose tissue, usually a decrease in leptin levels and, frequently, severe metabolic abnormalities including diabetes mellitus and dyslipidemia.
PURPOSE
To describe the clinical presentation of known types of lipodystrophy, and suggest specific steps to recognize, diagnose and treat lipodystrophy in the clinical setting.
METHODS
Based on literature and in our own experience, we propose a stepwise approach for diagnosis of the different subtypes of rare lipodystrophy syndromes, describing its more frequent co-morbidities and establishing the therapeutical approach.
RESULTS
Lipodystrophy is classified as genetic or acquired and by the distribution of fat loss, which can be generalized or partial. Genes associated with many congenital forms of lipodystrophy have been identified that may assist in diagnosis. Because of its rarity and heterogeneity, lipodystrophy may frequently be unrecognized or misdiagnosed, which is concerning because it is progressive and its complications are potentially life threatening. A basic diagnostic algorithm is proposed. Effective management of lipodystrophy includes lifestyle changes and aggressive, evidence-based treatment of comorbidities. Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval in Europe.
CONCLUSIONS
Here, we describe the clinical presentation of known types of lipodystrophy, present an algorithm for differential diagnosis of lipodystrophy, and suggest specific steps to recognize and diagnose lipodystrophy in the clinical setting.
Topics: Adipose Tissue; Diet, Healthy; Humans; Insulin Resistance; Leptin; Lipodystrophy; Treatment Outcome
PubMed: 29704234
DOI: 10.1007/s40618-018-0887-z -
The Journal of Clinical Investigation Oct 2019Over the past decade, great progress has been made in understanding the complexity of adipose tissue biology and its role in metabolism. This includes new insights into... (Review)
Review
Over the past decade, great progress has been made in understanding the complexity of adipose tissue biology and its role in metabolism. This includes new insights into the multiple layers of adipose tissue heterogeneity, not only differences between white and brown adipocytes, but also differences in white adipose tissue at the depot level and even heterogeneity of white adipocytes within a single depot. These inter- and intra-depot differences in adipocytes are developmentally programmed and contribute to the wide range of effects observed in disorders with fat excess (overweight/obesity) or fat loss (lipodystrophy). Recent studies also highlight the underappreciated dynamic nature of adipose tissue, including potential to undergo rapid turnover and dedifferentiation and as a source of stem cells. Finally, we explore the rapidly expanding field of adipose tissue as an endocrine organ, and how adipose tissue communicates with other tissues to regulate systemic metabolism both centrally and peripherally through secretion of adipocyte-derived peptide hormones, inflammatory mediators, signaling lipids, and miRNAs packaged in exosomes. Together these attributes and complexities create a robust, multidimensional signaling network that is central to metabolic homeostasis.
Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Exosomes; Humans; Insulin Resistance; Lipid Metabolism; Lipodystrophy; Metabolic Syndrome; MicroRNAs; Signal Transduction
PubMed: 31573548
DOI: 10.1172/JCI129187 -
Frontiers in Endocrinology 2022Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are essential to normal growth, metabolism, and body composition, but in acromegaly, excesses of these...
Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are essential to normal growth, metabolism, and body composition, but in acromegaly, excesses of these hormones strikingly alter them. In recent years, the use of modern methodologies to assess body composition in patients with acromegaly has revealed novel aspects of the acromegaly phenotype. In particular, acromegaly presents a unique pattern of body composition changes in the setting of insulin resistance that we propose herein to be considered an acromegaly-specific lipodystrophy. The lipodystrophy, initiated by a distinctive GH-driven adipose tissue dysregulation, features insulin resistance in the setting of reduced visceral adipose tissue (VAT) mass and intra-hepatic lipid (IHL) but with lipid redistribution, resulting in ectopic lipid deposition in muscle. With recovery of the lipodystrophy, adipose tissue mass, especially that of VAT and IHL, rises, but insulin resistance is lessened. Abnormalities of adipose tissue adipokines may play a role in the disordered adipose tissue metabolism and insulin resistance of the lipodystrophy. The orexigenic hormone ghrelin and peptide Agouti-related peptide may also be affected by active acromegaly as well as variably by acromegaly therapies, which may contribute to the lipodystrophy. Understanding the pathophysiology of the lipodystrophy and how acromegaly therapies differentially reverse its features may be important to optimizing the long-term outcome for patients with this disease. This perspective describes evidence in support of this acromegaly lipodystrophy model and its relevance to acromegaly pathophysiology and the treatment of patients with acromegaly.
Topics: Acromegaly; Adipokines; Ghrelin; Growth Hormone; Human Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Lipids; Lipodystrophy
PubMed: 36176462
DOI: 10.3389/fendo.2022.933039 -
Hormone Research in Paediatrics 2022Lipodystrophy includes a wide group of diseases characterized by reduction, absence, or altered distribution of adipose tissue. Lipodystrophies are classified into... (Review)
Review
BACKGROUND
Lipodystrophy includes a wide group of diseases characterized by reduction, absence, or altered distribution of adipose tissue. Lipodystrophies are classified into generalized or partial, according to the fat distribution, and congenital or acquired, considering the etiology.
SUMMARY
Impaired glucose and lipid metabolism are typically present, thus severe insulin resistance, diabetes mellitus, dyslipidemia, and hepatic steatosis are frequent complications. Because of the rarity and the diversification of lipodystrophies, diagnosis might be challenging, typically for partial forms that cannot be easily recognized, leading to progression of the several metabolic abnormalities associated. First management of lipodystrophy is diet and lifestyle changes, followed by the treatment of metabolic complications. Replacement therapy with metreleptin, currently available in the USA and Europe, has shown improvement of metabolic profile in a great number of patients with lipodystrophy.
KEY MESSAGES
The purpose of this review was to describe the phenotypic characteristics of all the known lipodystrophic types and to present specific steps for obtaining an early diagnosis and assessing the best treatment of lipodystrophy.
Topics: Adipose Tissue; Child; Fatty Liver; Glucose; Humans; Insulin Resistance; Lipodystrophy
PubMed: 35189617
DOI: 10.1159/000522620 -
Current Diabetes Reports Sep 2022Genetic or acquired lipodystrophies are characterized by selective loss of body fat along with predisposition towards metabolic complications of insulin resistance, such... (Review)
Review
PURPOSE OF REVIEW
Genetic or acquired lipodystrophies are characterized by selective loss of body fat along with predisposition towards metabolic complications of insulin resistance, such as diabetes mellitus, hypertriglyceridemia, hepatic steatosis, polycystic ovarian syndrome, and acanthosis nigricans. In this review, we discuss the various subtypes and when to suspect and how to diagnose lipodystrophy.
RECENT FINDINGS
The four major subtypes are autosomal recessive, congenital generalized lipodystrophy (CGL); acquired generalized lipodystrophy (AGL), mostly an autoimmune disorder; autosomal dominant or recessive familial partial lipodystrophy (FPLD); and acquired partial lipodystrophy (APL), an autoimmune disorder. Diagnosis of lipodystrophy is mainly based upon physical examination findings of loss of body fat and can be supported by body composition analysis by skinfold measurements, dual-energy x-ray absorptiometry, and whole-body magnetic resonance imaging. Confirmatory genetic testing is helpful in the proband and at-risk family members with suspected genetic lipodystrophies. The treatment is directed towards the specific comorbidities and metabolic complications, and there is no treatment to reverse body fat loss. Metreleptin should be considered as the first-line therapy for metabolic complications in patients with generalized lipodystrophy and for prevention of comorbidities in children. Metformin and insulin therapy are the best options for treating hyperglycemia and fibrates and/or fish oil for hypertriglyceridemia. Lipodystrophy should be suspected in lean and muscular subjects presenting with diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver disease, polycystic ovarian syndrome, or amenorrhea. Diabetologists should be aware of lipodystrophies and consider genetic varieties as an important subtype of monogenic diabetes.
Topics: Diabetes Mellitus; Female; Humans; Hypertriglyceridemia; Lipodystrophy; Lipodystrophy, Congenital Generalized; Magnetic Resonance Imaging; Polycystic Ovary Syndrome; Whole Body Imaging
PubMed: 35821558
DOI: 10.1007/s11892-022-01485-w -
Nucleus (Austin, Tex.) Jan 2018The nuclear lamina is a complex reticular structure that covers the inner face of the nucleus membrane in metazoan cells. It is mainly formed by intermediate filaments... (Review)
Review
The nuclear lamina is a complex reticular structure that covers the inner face of the nucleus membrane in metazoan cells. It is mainly formed by intermediate filaments called lamins, and exerts essential functions to maintain the cellular viability. Lamin A/C provides mechanical steadiness to the nucleus and regulates genetic machinery. Laminopathies are tissue-specific or systemic disorders caused by variants in LMNA gene (primary laminopathies) or in other genes encoding proteins which are playing some role in prelamin A maturation or in lamin A/C function (secondary laminopathies). Those disorders in which adipose tissue is affected are called laminopathic lipodystrophies and include type 2 familial partial lipodystrophy and certain premature aging syndromes. This work summarizes the main clinical features of these syndromes, their associated comorbidities and the clues for the differential diagnosis with other lipodystrophic disorders.
Topics: Adipose Tissue; Animals; Cell Nucleus; Humans; Lipodystrophy; Nuclear Lamina
PubMed: 29557732
DOI: 10.1080/19491034.2018.1454167 -
Frontiers in Endocrinology 2022Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including... (Review)
Review
Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance, that may lead to severe morbidity and, sometimes, mortality. Therefore, therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Given the evidence of leptin deficiency in lipodystrophy syndromes, leptin replacement therapy has been considered as a treatment option. Long-term studies on the use of therapy with a methionylated analog of human leptin, metreleptin, first on animals and subsequently on human patients, demonstrated enormous improvements of patients' clinical features and metabolic conditions. Recently, metreleptin was approved by Food and Drug Administration (FDA) for the treatment of generalized lipodystrophy and by European Medicines Agency (EMA) for the treatment of both generalized and partial lipodystrophy. However, further research is being conducted for new and different therapeutic agents, especially helpful for the treatment of patients with partial lipodystrophy, as some of them do not have access to metreleptin therapy or show poor response.
Topics: Animals; Humans; Insulin Resistance; Leptin; Lipodystrophy; Lipodystrophy, Congenital Generalized; United States
PubMed: 35600578
DOI: 10.3389/fendo.2022.879979 -
Frontiers in Endocrinology 2021Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic... (Review)
Review
Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed.
Topics: Adipocytes; Adipose Tissue; Aging, Premature; Humans; Inflammation; Insulin Resistance; Leptin; Lipodystrophy; Lipomatosis; Syndrome
PubMed: 35046902
DOI: 10.3389/fendo.2021.803189