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Lipodystrophy

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3. Metreleptin (Myalepta) - Lipodystrophy, Familial Partial

Metreleptin (Myalepta) - Lipodystrophy, Familial Partial 30 Churchill Place ? Canary Wharf ? London E14 5EU ? United Kingdom An agency of the European Union Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. EMA/386898/2018 EMEA/H/C/004218 Myalepta (metreleptin) An overview of Myalepta and why it is authorised in the EU What (...) is Myalepta and what is it used for? Myalepta is a medicine 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 2 years with generalised (throughout the body) lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome); • adults and children above the age of 12 years with partial (localised) lipodystrophy

2018 European Medicines Agency - EPARs

4. Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy? (PubMed)

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy? Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy (...) is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment. Research carried out showed that FGF21 levels were significantly increased in untreated HIV-1-infected patients and the increase was much marked in HIV-1-infected antiretroviral-treated patients that have developed lipodystrophy and in the patients with greatest metabolic alterations. FGF21 is expressed mainly by the liver, but also by other tissues such as the thymus

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2016 Journal of translational internal medicine

5. Clinical Characteristics, Phenotype of Lipodystrophy and a Genetic Analysis of Six Diabetic Japanese Women with Familial Partial Lipodystrophy in a Diabetic Outpatient Clinic (PubMed)

Clinical Characteristics, Phenotype of Lipodystrophy and a Genetic Analysis of Six Diabetic Japanese Women with Familial Partial Lipodystrophy in a Diabetic Outpatient Clinic Objective Our aim was to examine the clinical characteristics and phenotype of lipodystrophy of six diabetic Japanese women with partial lipodystrophy (PL) who received a genetic analysis at a diabetic outpatient clinic. Methods We screened for PL using dual energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (...) lipodystrophy (FPLD). They all had near-complete loss of subcutaneous fat, particularly in the antero-lateral and posterior thigh region and the calf region. As almost all patients were characterized by fat loss in the lower limbs with abdominal fat accumulation, a high rate of positivity for a family history, diabetes, and an unknown genetic cause, we suspected they might have FPLD1. Some patients have shown relatively severe insulin resistance, while others have shown insulin deficiency. Four and one had

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2018 Internal Medicine

6. Lipodystrophy Increases the Risk of CKD Development in HIV-Positive Patients in Switzerland: The LIPOKID Study (PubMed)

Lipodystrophy Increases the Risk of CKD Development in HIV-Positive Patients in Switzerland: The LIPOKID Study Antiretroviral therapy has improved the life expectancy of patients living with HIV. However, lipodystrophy syndrome (LD) remains prevalent, affecting mostly patients treated with first-generation antiretroviral drugs. This syndrome is characterized by changes in body fat distribution with or without associated metabolic changes. Here, we studied whether clinically evaluated LD

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2018 Kidney international reports

7. Congenital Generalized Lipodystrophy Type 2 in a Patient From a High-Prevalence Area (PubMed)

Congenital Generalized Lipodystrophy Type 2 in a Patient From a High-Prevalence Area Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease characterized by the loss of body fat. The global prevalence of CGL is one in 10 million, and there are four subtypes. The case is presented of a 18-year-old woman from rural area of the north coast of Peru (Piura) with limited access to health services. She was diagnosed with phenotypic CGL at age 7 months. At age 12 years, she

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2017 Journal of the Endocrine Society

8. Correction to: Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C. (PubMed)

Correction to: Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C. The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

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2019 Diabetologia

9. Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy. (PubMed)

Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy. Interleukin (IL)-18 is involved in regulation of lipid and glucose metabolism. Mice lacking whole-body IL-18 signalling are prone to develop weight gain and insulin resistance, a phenotype which is associated with impaired fat oxidation and ectopic skeletal muscle lipid deposition. IL-18 mRNA is expressed in human skeletal muscle (...) but a role for IL-18 in muscle has not been identified. Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and glucose disturbances and increased levels of circulating IL-18. We hypothesized that skeletal muscle IL-18 and IL-18 receptor (R) expression would be altered in patients with HIV-lipodystrophy.Twenty-three HIV-infected patients with LD and 15 age-matched healthy controls were included in a cross-sectional study. Biopsies from the vastus lateralis muscle were obtained

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2018 PLoS ONE

10. Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy. (PubMed)

Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy. Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease that affects the development of adipocytes and leads to an inability to store fat in adipocytes. This study aimed to evaluate the life expectancy and the causes of death of patients with BSCL.We analyzed death certificates, and medical records of BSCL patients who died between 1997 and 2017. If the death certificate

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2018 PLoS ONE

11. Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice. (PubMed)

Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice. The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis

2019 International Journal of Obesity

12. Acquired Lipodystrophy Associated with Nivolumab in a Patient with Advanced Renal Cell Carcinoma. (PubMed)

Acquired Lipodystrophy Associated with Nivolumab in a Patient with Advanced Renal Cell Carcinoma. Lipodystrophy syndromes are rare disorders characterized by the selective loss of adipose tissue. We aimed to report the first case of acquired generalized lipodystrophy possibly associated with nivolumab.A woman was referred to our Endocrinology Department for uncontrolled diabetes mellitus. At 50 years of age, she was diagnosed with type 2 diabetes after a routine laboratory test and her diabetes (...) 1.5 units/kg/day insulin. Subcutaneous biopsy of medial surface of the arm revealed chronic lobular panniculitis. Despite nivolumab's possible involvement in the onset of lipodystrophy, the maintenance of nivolumab therapy was justified by the observed reduction in the progression of the cancer, combined with the lack of an alternative chemotherapy. The therapy was withdrawn after eight months of treatment because of grade 3 hepatitis.Anti-PD1 therapy has great potential. Early recognition

2019 Journal of Clinical Endocrinology and Metabolism

13. Recurrent fevers, progressive lipodystrophy, and annular plaques in a child. (PubMed)

Recurrent fevers, progressive lipodystrophy, and annular plaques in a child. KEY TEACHING POINTS.Published by Elsevier Inc.

2019 Journal of the American Academy of Dermatology

14. Effects of metreleptin on proteinuria in patients with lipodystrophy. (PubMed)

Effects of metreleptin on proteinuria in patients with lipodystrophy. Patients with lipodystrophy have high prevalence of proteinuria.To assess kidney disease in patients with generalized (GLD) versus partial lipodystrophy (PLD), and effects metreleptin on proteinuria in patients with lipodystrophy.Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health, Bethesda, MD.24-hour urinary albumin and protein excretion rates, estimated (...) significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment.Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD versus PLD but did

2019 Journal of Clinical Endocrinology and Metabolism

15. Acquired generalized lipodystrophy under immune checkpoint inhibition. (PubMed)

Acquired generalized lipodystrophy under immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now the standard of care in the treatment of several cancer types. Cutaneous immune-related adverse events (irAEs) are usually of low grade and reversible, while endocrine irAEs are generally irreversible and managed with hormone replacement therapy. We report a 47-year-old patient treated with the anti-programmed cell death 1 (anti-PD1) antibody pembrolizumab for a metastatic melanoma (...) who developed severe lipodystrophy after 10 months of treatment, characterized by the loss of subcutaneous fat tissue, central obesity and insulin resistance with a decreased leptin level. Histologic analysis of a cutaneous biopsy revealed subcutaneous fat cell destruction associated with oedema, the presence of lipophages, and T-CD3+ lymphocytic infiltrate involving the panniculus, leading to the diagnosis of anti-PD-1-induced acquired generalized lipodystrophy after ruling out differential

2019 British Journal of Dermatology

16. Natural course of NAFLD and type 2 diabetes in HIV-positive subjects with and without combination antiretroviral therapy (cART)-associated lipodystrophy: a 16-year follow-up study. (PubMed)

Natural course of NAFLD and type 2 diabetes in HIV-positive subjects with and without combination antiretroviral therapy (cART)-associated lipodystrophy: a 16-year follow-up study. Abnormal glucose metabolism and non-alcoholic fatty liver disease (NAFLD) are common in HIV-positive (HIV+) subjects but longitudinal data are lacking. We determined the natural course of NAFLD (liver fat, LFAT) and type 2 diabetes (T2DM) in HIV+ subjects with and without lipodystrophy (LD) during a 16-year

2019 Clinical Infectious Diseases

17. Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study. (PubMed)

Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study. Adiponectin levels are inversely related to cardiovascular risk and are low in diabetics and obese persons. We examined the association between adiponectin concentration and HIV-associated lipodystrophy, which remains unclear.The Study to Understand the Natural History of HIV/AIDS in the Era of Effective (...) Therapy (SUN) was a prospective cohort study of HIV-infected adults conducted in four US cities. Lean body and fat masses were assessed using dual-energy X-ray absorptiometry scans. Using baseline data from 2004 to 2006, we defined lipodystrophy using a sex-specific fat mass ratio and performed cross-sectional analyses of associated risks using multivariable logistic regression.Among 440 male participants (median age 42 years; 68% non-Hispanic white; 88% prescribed combination antiretroviral therapy

2019 HIV medicine

18. Diagnostic challenge in PLIN1-associated Familial Partial Lipodystrophy. (PubMed)

Diagnostic challenge in PLIN1-associated Familial Partial Lipodystrophy. Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only 6 families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and/or hyperinsulinemia was recently questioned based on the absence (...) of lipodystrophy in these individuals and on the elevated frequency of PLIN1 null variants in the general population.To reevaluate the pathogenicity of PLIN1 frameshift variants in light of new data obtained in the largest series of patients with FPLD4.We performed histological, and molecular studies in patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and/or insulin resistance, and carrying PLIN1 frameshift variants.We

2019 Journal of Clinical Endocrinology and Metabolism

19. Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes. (PubMed)

Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes. Anti-programmed cell death-1 (anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD-1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations, including acute-onset type 1 diabetes. Acquired generalized lipodystrophy (AGL) is a rare disease, believed to be immune mediated, characterized by loss of adipose tissue and insulin resistance-associated

2019 Diabetes Care

20. Recent developments in lipodystrophy. (PubMed)

Recent developments in lipodystrophy. Lipodystrophy syndromes have an estimated prevalence of 1.3-4.7 cases per million and as with other rare diseases conducting research can be challenging. The present review highlights recently published work that has provided insights into the field of non-HIV--associated lipodystrophy syndromes.Lipodystrophies are a heterogenous group of disorders, as such research is often focused on specific subtypes of the condition. The identification of children (...) carrying LMNA mutations has provided insights into the natural history of FPLD2, specifically that the adipose tissue phenotype predates the onset of puberty. Recent reports of PLIN1 heterozygous null variant carriers and the apparent absence of a lipodystrophy phenotype challenges our understanding of the molecular biology of perilipin 1 and its role in the pathogenesis of FPLD4. With a focus on therapeutics, studies delineating the differential responsiveness of PPARγ mutants to endogenous

2019 Current Opinion in Lipidology

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