The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Bente Klarlund Pedersen - One of the best experts on this subject based on the ideXlab platform.
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acute reduction of lipolysis reduces adiponectin and il 18 evidence from an intervention study with acipimox and insulin
Diabetologia, 2013Co-Authors: Birgitte Lindegaard, Susanne Ditlevsen, Peter Plomgaard, B Mittendorfer, Bente Klarlund PedersenAbstract:Aims/hypothesis Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and Lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with Lipodystrophy.
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the effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus infected patients with Lipodystrophy
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Birgitte Lindegaard, Susanne Ditlevsen, Peter Plomgaard, Torben Hansen, Thine Hvid, G Van Hall, J Gerstoft, Bente Klarlund PedersenAbstract:Context: Fat redistribution, insulin resistance, and low-grade inflammation characterize HIV-infected patients with Lipodystrophy. Currently, no effective therapies exist for the combined treatment of fat redistribution and insulin resistance. Objective: Our objective was to evaluate the effects of strength and endurance training on insulin sensitivity and fat distribution in HIV-infected patients with Lipodystrophy. Subjects and Methods: Twenty sedentary HIV-infected men with Lipodystrophy were randomly assigned to supervised strength or endurance training three times a week for 16 wk. The primary endpoints were improved peripheral insulin sensitivity (euglycemic-hyperinsulinemic clamp combined with isotope-tracer infusion) and body fat composition (dual-energy x-ray absorptiometry scan). Secondary endpoints included fasting lipids and inflammatory markers. Results: Insulin-mediated glucose uptake increased with both endurance training (55.7 ± 11 to 63.0 ± 11 μmol glucose/kg lean mass·min, P = 0.02) and ...
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low plasma level of adiponectin is associated with stavudine treatment and Lipodystrophy in hiv infected patients
Clinical and Experimental Immunology, 2004Co-Authors: Birgitte Lindegaard, Pernille Keller, Helle Bruunsgaard, Jan Gerstoft, Bente Klarlund PedersenAbstract:This study tested the hypothesis that in patients with HIV-associated Lipodystrophy, adiponectin levels were related to insulin resistance, TNF-alpha and IL-6 and treatment with nucleoside analogues. HIV seropositive men undergoing highly active antiretroviral treatment were enrolled into three predetermined clinical groups: Lipodystrophy with central fat accumulation (n = 12); Lipodystrophy without central fat accumulation (n = 15); no Lipodystrophy (n = 15). HIV-negative healthy men served as controls (n = 12). Both lipodystrophic groups had a low percentage of limb fat compared to the two control groups. Patients with Lipodystrophy with fat accumulation had increased truncal fat compared with controls. Levels of adiponectin did not correlate with either TNF-alpha or IL-6. Low levels of adiponectin were found in both lipodystrophic groups and were associated with current or previous treatment with stavudine. Furthermore, the adiponectin level correlated with the percentage of limb fat. Patients with Lipodystrophy with fat accumulation were more insulin resistant, measured by HOMA-IR, compared with controls. However, HOMA-IR did no correlate to adiponectin or other cytokines. In conclusion, the finding of no difference between the two lipodystrophic groups with regard to adiponectin, indicates that low levels of adiponectin reflects fat atrophy, whereas the insulin resistance was best explained by increased truncal fat mass.
David A Cooper - One of the best experts on this subject based on the ideXlab platform.
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reversibility of lipoatrophy in hiv infected patients 2 years after switching from a thymidine analogue to abacavir the mitox extension study
AIDS, 2004Co-Authors: Allison Martin, Andrew Carr, Sean Emery, Don Smith, Clare Ringland, Janaki Amin, Cassy Workman, Nicholas Doong, Judith Freund, David A CooperAbstract:OBJECTIVE: To determine if long-term improvement in HIV lipoatrophy can be attained by substitution of thymidine analogues zidovudine (ZDV) or stavudine (d4T) with abacavir (ABC). DESIGN: Long-term follow-up (104 weeks) of a randomized, open-label study. SETTING: Seventeen ambulatory HIV clinics in Australia and London. SUBJECTS: Patients with HIV Lipodystrophy were randomized to switch from a thymidine analogue to ABC, while continuing all other antiretroviral therapy (ABC arm) (n = 42) or continue current therapy (ZDV/d4T arm) (n = 43). INTERVENTION: At week 24, all control patients could switch to ABC. Of the original 111 patients randomized, 85 had long-term follow-up data, with 77 having imaging data available at 104 weeks. MAIN OUTCOME MEASURE: The primary endpoint was time-weighted change in limb fat mass, measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: At week 104, the mean increase in limb fat for the ABC and ZDV/d4T group was 1.26 +/- 2.02 kg and 0.49 +/- 1.38 kg, respectively. The time-weighted change for limb fat was significantly different between the two arms (0.43 kg; P = 0.008). On-treatment analysis demonstrated a trend for increased limb fat in patients in the ABC arm. Visceral fat accumulation, buffalo hump, self-assessed Lipodystrophy or the Lipodystrophy case definition score (LCDS) did not improve. CONCLUSIONS: In patients with moderate-to-severe Lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC. Nevertheless, the Lipodystrophy syndrome was still evident, indicating additional strategies need evaluating.
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hiv Lipodystrophy prevalence severity and correlates of risk in australia
Hiv Medicine, 2003Co-Authors: John Miller, Andrew Carr, Sean Emery, Matthew Law, S Mallal, Dewleen G Baker, Don Smith, John M Kaldor, David A CooperAbstract:Objective To establish the prevalence, severity and factors associated with the HIV Lipodystrophy syndrome. Methods Cross-sectional study of Lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with Lipodystrophy, lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. Results One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/μL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral lipoatrophy and central lipohypertrophy, 31% experienced peripheral lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of Lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. Conclusions The prevalence and severity of Lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of Lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic lipoatrophy and lipohypertrophy, respectively.
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diagnosis prediction and natural course of hiv 1 protease inhibitor associated Lipodystrophy hyperlipidaemia and diabetes mellitus acohort study
The Lancet, 1999Co-Authors: Andrew Carr, Katherine Samaras, Donald J Chisholm, David A Cooper, Anna Thorisdottir, Gilbert R KaufmannAbstract:BACKGROUND The prevalence and severity of Lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. METHODS We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. FINDINGS There was 98% concordance between patients' reports of the presence or absence of Lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naive patients; p=0.0001) and physical examination. Patients' ratings of Lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe Lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naive patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. INTERPRETATION Diagnosis and rating severity of Lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict Lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.
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a syndrome of peripheral Lipodystrophy hyperlipidaemia and insulin resistance in patients receiving hiv protease inhibitors
AIDS, 1998Co-Authors: Andrew Carr, Katherine Samaras, Donald J Chisholm, Samantha Burton, J Freund, David A CooperAbstract:Objective: To describe a syndrome of peripheral Lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. Design: Cross-sectional study. Setting: Outpatient clinic of a university teaching hospital. Patients: HlV-infected patients either receiving at least one protease inhibitor (n = 116) or protease inhibitor-naive (n = 32), and healthy men (n = 47). Interventions and main outcome measures: Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. Results: HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P = 0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P = 0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with Lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without Lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to Lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. Conclusion: A syndrome of peripheral Lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.
Birgitte Lindegaard - One of the best experts on this subject based on the ideXlab platform.
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acute reduction of lipolysis reduces adiponectin and il 18 evidence from an intervention study with acipimox and insulin
Diabetologia, 2013Co-Authors: Birgitte Lindegaard, Susanne Ditlevsen, Peter Plomgaard, B Mittendorfer, Bente Klarlund PedersenAbstract:Aims/hypothesis Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and Lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with Lipodystrophy.
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the effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus infected patients with Lipodystrophy
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Birgitte Lindegaard, Susanne Ditlevsen, Peter Plomgaard, Torben Hansen, Thine Hvid, G Van Hall, J Gerstoft, Bente Klarlund PedersenAbstract:Context: Fat redistribution, insulin resistance, and low-grade inflammation characterize HIV-infected patients with Lipodystrophy. Currently, no effective therapies exist for the combined treatment of fat redistribution and insulin resistance. Objective: Our objective was to evaluate the effects of strength and endurance training on insulin sensitivity and fat distribution in HIV-infected patients with Lipodystrophy. Subjects and Methods: Twenty sedentary HIV-infected men with Lipodystrophy were randomly assigned to supervised strength or endurance training three times a week for 16 wk. The primary endpoints were improved peripheral insulin sensitivity (euglycemic-hyperinsulinemic clamp combined with isotope-tracer infusion) and body fat composition (dual-energy x-ray absorptiometry scan). Secondary endpoints included fasting lipids and inflammatory markers. Results: Insulin-mediated glucose uptake increased with both endurance training (55.7 ± 11 to 63.0 ± 11 μmol glucose/kg lean mass·min, P = 0.02) and ...
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low plasma level of adiponectin is associated with stavudine treatment and Lipodystrophy in hiv infected patients
Clinical and Experimental Immunology, 2004Co-Authors: Birgitte Lindegaard, Pernille Keller, Helle Bruunsgaard, Jan Gerstoft, Bente Klarlund PedersenAbstract:This study tested the hypothesis that in patients with HIV-associated Lipodystrophy, adiponectin levels were related to insulin resistance, TNF-alpha and IL-6 and treatment with nucleoside analogues. HIV seropositive men undergoing highly active antiretroviral treatment were enrolled into three predetermined clinical groups: Lipodystrophy with central fat accumulation (n = 12); Lipodystrophy without central fat accumulation (n = 15); no Lipodystrophy (n = 15). HIV-negative healthy men served as controls (n = 12). Both lipodystrophic groups had a low percentage of limb fat compared to the two control groups. Patients with Lipodystrophy with fat accumulation had increased truncal fat compared with controls. Levels of adiponectin did not correlate with either TNF-alpha or IL-6. Low levels of adiponectin were found in both lipodystrophic groups and were associated with current or previous treatment with stavudine. Furthermore, the adiponectin level correlated with the percentage of limb fat. Patients with Lipodystrophy with fat accumulation were more insulin resistant, measured by HOMA-IR, compared with controls. However, HOMA-IR did no correlate to adiponectin or other cytokines. In conclusion, the finding of no difference between the two lipodystrophic groups with regard to adiponectin, indicates that low levels of adiponectin reflects fat atrophy, whereas the insulin resistance was best explained by increased truncal fat mass.
Aminata Diack - One of the best experts on this subject based on the ideXlab platform.
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Low prevalence of Lipodystrophy in HIV-infected Senegalese children on long-term antiretroviral treatment: the ANRS 12279 MAGGSEN Pediatric Cohort Study
BMC Infectious Diseases, 2018Co-Authors: Cecile Cames, Lea Pascal, Hélène Mbodj, Baly Ouattara, Ndeye-fatou Diallo, Philippe Msellati, Ngagne Mbaye, Haby Sy Signate, Stéphane Blanche, Aminata DiackAbstract:BACKGROUND: The long-term benefits of antiretroviral treatment (ART) are associated with metabolic complications, especially Lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of Lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART. The objectives of this cross-sectional analysis are to assess and identify risk factors affecting the prevalence of Lipodystrophy in Senegalese children and adolescents on long-term ART participating in a cohort study. METHODS: Lipodystrophy was clinically assessed in two- to 18-year-old children on ART for at least six months and with no concurrent severe acute malnutrition. Risk factors for Lipodystrophy were identified using stepwise multivariable logistic regression. Explanatory variables included clinical and personal data, immunovirologic status, and therapeutic history. RESULTS: Overall, 254 children were assessed for Lipodystrophy. The median age was 10.9 years (IQR: 8.1-14.2) and the median duration on ART was 54 months (32-84). Only 18% had been previously treated with stavudine, with a median treatment duration of 8 months (5-25). Ongoing treatment included 76% of children receiving zidovudine (median duration of 48 months (26-74)) and 27% receiving PI (lopinavir/ritonavir; median duration of 49 months (23-59)). Mild signs of Lipodystrophy were observed in 33 children (13%): 28 with lipoatrophy, 4 with lipohypertrophy and one with combined type. Boys were more likely to present with lipoatrophy than girls (aOR: 4.3, 95% CI: 1.6-11.7). Children previously treated with stavudine for ≥1 year had a greater risk for lipoatrophy than those never exposed (3.8, 1.0-14.0), although the association was weak. There was no association between Lipodystrophy and age or current or cumulative treatment with lopinavir/ritonavir or zidovudine. CONCLUSIONS: We report low prevalence of mild Lipodystrophy in children and adolescents on long-term ART receiving a stavudine-sparing regimen. These findings are reassuring for clinicians in low-income settings where zidovudine is massively prescribed and lopinavir/ritonavir is the only widely available PI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01771562 (registration date: 01/18/2013).
Baris Akinci - One of the best experts on this subject based on the ideXlab platform.
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european Lipodystrophy registry background and structure
Orphanet Journal of Rare Diseases, 2020Co-Authors: Julia Von Schnurbein, Claire Adams, Baris Akinci, Giovanni Ceccarini, Maria Rosaria Dapice, Alessandra Gambineri, Raoul C M Hennekam, Isabelle Jeru, Giovanna Lattanzi, Konstanze MiehleAbstract:Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each Lipodystrophy subform, research in this area is difficult and international co-operation mandatory. Therefore, in 2016, the European Consortium of Lipodystrophies (ECLip) decided to create a registry for patients with Lipodystrophy. The registry was build using the information technology Open Source Registry System for Rare Diseases in the EU (OSSE), an open-source software and toolbox. Lipodystrophy specific data forms were developed based on current knowledge of typical signs and symptoms of Lipodystrophy. The platform complies with the new General Data Protection Regulation (EU) 2016/679 by ensuring patient pseudonymization, informational separation of powers, secure data storage and security of communication, user authentication, person specific access to data, and recording of access granted to any data. Inclusion criteria are all patients with any form of Lipodystrophy (with the exception of HIV-associated Lipodystrophy). So far 246 patients from nine centres (Amsterdam, Bologna, Izmir, Leipzig, Munster, Moscow, Pisa, Santiago de Compostela, Ulm) have been recruited. With the help from the six centres on the brink of recruitment (Cambridge, Lille, Nicosia, Paris, Porto, Rome) this number is expected to double within the next one or 2 years. A European registry for all patients with Lipodystrophy will provide a platform for improved research in the area of Lipodystrophy. All physicians from Europe and neighbouring countries caring for patients with Lipodystrophy are invited to participate in the ECLip Registry. ClinicalTrials.gov (NCT03553420). Registered 14 March 2018, retrospectively registered.
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phenotypic and genetic characteristics of Lipodystrophy pathophysiology metabolic abnormalities and comorbidities
Current Diabetes Reports, 2018Co-Authors: Baris Akinci, Rasimcan Meral, Elif A OralAbstract:This article focuses on recent progress in understanding the genetics of Lipodystrophy syndromes, the pathophysiology of severe metabolic abnormalities caused by these syndromes, and causes of severe morbidity and a possible signal of increased mortality associated with Lipodystrophy. An updated classification scheme is also presented. Lipodystrophy encompasses a group of heterogeneous rare diseases characterized by generalized or partial lack of adipose tissue and associated metabolic abnormalities including altered lipid metabolism and insulin resistance. Recent advances in the field have led to the discovery of new genes associated with Lipodystrophy and have also improved our understanding of adipose biology, including differentiation, lipid droplet assembly, and metabolism. Several registries have documented the natural history of the disease and the serious comorbidities that patients with Lipodystrophy face. There is also evolving evidence for increased mortality rates associated with Lipodystrophy. Lipodystrophy syndromes represent a challenging cluster of diseases that lead to severe insulin resistance, a myriad of metabolic abnormalities, and serious morbidity. The understanding of these syndromes is evolving in parallel with the identification of novel disease-causing mechanisms.
