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PubMed2003

Practical applications of the HIV lipodystrophy case definition.

Diagnosis of HIV-associated lipodystrophy (LD) has been limited by the absence of a validated case definition and the frequent lack of objective body composition measures. An international, objective, case-control study recruited HIV-infected, adult outpatients free of active AIDS, and a case definition model for LD was developed. The relative merits and limitations of this definition as a practical tool for the long-term monitoring of a patient's LD status over the duration of clinical treatment are discussed.

Adult↗
PubMedDate not supplied

A case of membranous lipodystrophy with skeletal involvement.

It is the purpose of this study to describe the orthopaedic features of Nasu disease or membranous lipodystrophy based on the observation of a rare clinical case of the pathology and on a review of the international literature. The case described is probably the first to have been observed in Italy, and may be added to the 80 cases currently known to exist the world over. The disease affects young adults and involves pathologic fractures, as well as psychological and neurological disorders. It is currently of unknown etiology and its course is progressive until the death of the subject. The radiological aspect shows metaepiphyseal polycystic lesions of the long bones, with a tendency to expand, and involvement of the cortex. Causal treatment of the disease is currently not possible. The authors emphasize that differential diagnosis involving other diseases having a similar anatomopathological picture may be obtained, and they propose several suggestions for orthopaedic treatment based on their own experience.

Adult↗
PubMed2004

[Lipodystrophy and lipid metabolism alterations in HIV-infected patients receiving highly active antiretroviral therapy (HAART)].

A wide range of morphologic alterations and lipid metabolism abnormalities have been recently described in HIV-infected patients receiving a protease inhibitor-based highly active antiretroviral therapy. The hyperlipidaemia may involve up to 70-80% of HIV-positive subjects treated with a protease inhibitor-containing regimen, and it is frequently (but not always) associated with the fat redistribution syndrome or lipodystrophy. The potential clinico-pathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations reported an increased risk of prematury coronary artery diseases in young HIV-positive individuals receiving protease inhibitors, besides peripheral atherosclerosis and acute pancreatitis. A hypolipidaemic diet and regular physical exercise may act favourably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or pesists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

[Outcome of hyperlactatemia and lipodystrophy syndromes in patients infected with human immunodeficiency virus].

HIV-positive persons requiring a highly active antiretroviral therapy containing one or more nucleosidic reverse transcriptase inhibitors associated with or without protease inhibitors are exposed to metabolic side effects among which lipodystrophy and hyperlactemia, defined by blood lactates higher than 2,25 mmol/L. Hyperlactatemia had to be differentiated from lactic acidosis of type B (without hypoxemia, lactates higher than 5 mmol/L and arterial pH lower than 7,3), a rare but potentially fatal complication by multi-visceral failure. The accused INRT induce mitochondrial toxicity by inhibition of DNA gamma polymerase and deterioration of its DNA. Our exploratory study, troop of 282 patients, identified age and stavudine like statistically associated, which has occurred of this metabolic anomaly. The patients having profited of a therapeutic change with the profit from drugs minus hyperlactatogenic presented an obvious clinical and biological improvement; whereas similar switch of therapy occurred for the lipodystrophic patients presented any clinical improvement. Nevertheless, biological parameters (blood lactates, triglycerides, total cholesterol and LDL-cholesterol) were significantly decreased after this therapeutic switch occurred on the lipodystrophic patients. In conclusion, the measurement of the following biological parameters: glycemia, lactatemia, triglycerides, total cholesterol and LDL-cholesterol at patient VIH, in a simple and rigorous pre-analytical and analytical context, appears to us justified in the monitoring of metabolic disorders in treated HIV patients by INRT and/or IP.

Acidosis, Lactic↗
PubMed2004

Comparison of dual-energy X-ray absorptiometry machines for measuring fat distribution changes of HIV-associated lipodystrophy.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is regarded as a useful objective method for diagnosis of HIV-associated lipodystrophy (LD). OBJECTIVE: To determine whether the use of different DXA machines may affect the diagnosis of LD. METHODS: Body composition in 24 HIV-infected patients, 12 of whom had clinically diagnosed LD, was measured on two DXA machines (Lunar and Hologic). RESULTS: Hologic gave significantly higher values than Lunar DXA for total body fat percent (22.9 vs 20.5%, P<0.001), arm fat percent (27.9 vs 14.5%, P<0.001) and leg fat percent (23.4 vs 17.5%, P<0.001), and significantly lower values than Lunar for trunk fat percent (22.3 vs 24.7%, P<0.001) and trunk-to-limb fat percent ratio (0.89 vs 1.62, P<0.001). When measured by Lunar, patients with LD had significantly lower leg fat percent (13.5 vs 21.6%, P=0.04) and higher trunk-to-limb fat percent ratio (1.85 vs 1.38; P=0.012) than those without LD. When measured by Hologic, patients with LD had values of leg fat percent (20.1 vs 26.8%, P=0.11) and trunk-to-limb fat percent ratio (0.95 vs 0.85, P=0.43) that did not differ significantly from those without LD. There was a significant difference in the contribution to a composite LD score between Lunar and Hologic measurements. CONCLUSION: DXA machines from different manufacturers give major differences in measurements of body fat content and distribution, and this may affect the ability to distinguish patients with LD from those without LD. Further standardization of DXA technology is needed before widespread application in the clinical diagnosis of LD.

Absorptiometry, Photon↗
PubMed2005

Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis.

HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV-LD were compared with HIV-infected subjects without LD and subjects without HIV disease. Although apoptosis was observed in subjects with HIV-LD, there was no difference in the incidence of individuals with apoptosis among those with HIV-LD (10 of 22 subjects), those with HIV but no LD (13 of 25 subjects), and those without HIV disease (13 of 27 subjects). These data suggest that HIV-related chronic loss of SAT may not always be associated with increased frequency of adipocyte apoptosis.

Adipocytes↗
PubMed2005

Mitochondrial studies in HAART-related lipodystrophy: from experimental hypothesis to clinical findings.

Chronic use of antiretrovirals (ARVs) to treat HIV infection, along with more prolonged patient survival, has been associated with an increase in adverse drug effects in HIV-infected patients on treatment. It has been proposed that some of these adverse effects (including myopathy, cardiomyopathy, anaemia, hyperlactataemia/ lactic acidosis, pancreatitis, polyneuritis and lipodystrophy) could be mediated by mitochondrial (mt) toxicity. From the experimental data, it has been proposed that nucleoside analogue reverse transcriptase inhibitors (NRTIs) also inhibit gamma-polymerase, the enzyme devoted to replicate (and, to a lesser extent, repair) mtDNA. It is now widely accepted that the use of most NRTIs in HIV-infected patients is associated with mtDNA depletion. Although cross-sectional studies suggest that certain ARVs, especially stavudine, are more toxic to mitochondria, the differences among different highly active ARV therapy (HAART) schedules detected in the analysis of longitudinal studies are not so clear. These types of study in previously untreated individuals suggest that the greatest mtDNA loss appears at the beginning of the treatment. Conversely, in ARV-experienced patients, the potential beneficial effects of HAART changes in terms of mtDNA content remain controversial and must be further investigated. Functional studies accompanying genetic investigations are needed for the correct pathogenic interpretation of the mtDNA abnormalities.

Antiretroviral Therapy, Highly Active↗
PubMed1992

Membranous lipodystrophy. Clinical and electrophysiological observations in the first South African case.

A 37-year-old white man with membranous lipodystrophy (ML), the first case from Africa, is reported. Two years before presentation a diagnosis of presenile dementia of uncertain aetiology had been made. The diagnosis of ML was confirmed on histological examination of bone fragments obtained during surgery for reduction of pathological fractures. Computed tomography of the head showed typical cerebral atrophy and basal ganglia calcification. Electrophysiological observations included normal peripheral and central conduction studies.

Adult↗
PubMed2005

HIV--associated lipodystrophy in children.

Lipodystrophy (LD) with varying degrees of lipohypertrophy, lipoatrophy, hyperlipidemia, and insulin resistance is one of the complications of highly active antiretroviral therapy (HAART) and occurs in one to 33 % of HAART-treated, HIV infected children. We summarize the data on the role of leptin, adiponectin, the growth hormone axis, glucocorticoids, sterol response element binding protein 1c (SREBP-1c), the tumor necrosis factor alpha axis (TNF-alpha), interleukin-6 (IL-6), interleukin- 18 (IL-18), interferon-alpha (IFN-alpha), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1) in the pathophysiology of LD. Adiponectin levels are generally decreased in LD, whereas leptin levels are increased. Systemic cortisol levels are not elevated in LD, even though glucocorticoids seem to play an important role in LD and the phenotype can be reminiscent of Cushing syndrome. GH resistance in LD needs to be better characterized. While some cytokines show promise as markers for LD, it is difficult to tell whether their derangement is a cause of or the effect of LD.

Adiponectin↗
PubMed2005

[Prevention and therapy of HIV-associated lipodystrophy syndrome and antiretroviral caused metabolic changes].

Metabolic changes and lipodystrophy in HIV patients are sequelae of antiretroviral therapy, although the pathophysiology is, in part, still not well understood. These thoughts should be taken into consideration in making the decision for beginning therapy; however, they should be regarded as having lower priority when immunosuppression is clearly present since the clinical significance of many changes is not certain at this time. Numerous therapy recommendations are presently insufficiently evidence-based or are experimental. Treatment in connection with clinical studies or within the scope of a documented application is desirable. In any case, whether the probable long-term damage through HAART caused metabolic changes justifies a therapeutic intervention with likewise potential toxicity should be carefully deliberated.

Anti-HIV Agents↗
PubMed2006

[Metabolic abnormalities, lipodystrophy and cardiovascular risk in HIV-infected patients].

Life expectancy of HIV-infected patients has improved considerably with HAART. However long term use of HAART is linked with lipodystrophy syndrom (subcutaneous lipoatrophy and central fat accumulation) associated with dyslipemia (hypoHDL, hyperLDL and hypertriglyceridemia) and insulin resistance. It is also linked with mitochondrial toxicity clinically expressed by chronic fatigue syndrom and premature aging. The induced metabolic syndrom has cardiovascular consequences and myocardial infarction is the cause of 7% of the HIV-infected deaths in 2000. Assessment of these complications should be done at least every year. Treatment options concern antiretroviral therapy with the search for the least toxic drug (but with equal antiviral efficacy), symptomatic treatment (statin, fibrates, thiazolidinediones, metformin) and lifestyle modifications (first of all, stopping cigarette smoking!)

Antiretroviral Therapy, Highly Active↗
PubMed1990

Generalised lipodystrophy.

We report a Malay girl suffering from generalised lipodystrophy, with clinical features of absence of body adipose tissue, hepatomegaly, hyperpigmentation and muscular hypertrophy. She also had hyperlipaemia, hypercholesterolemia and non-ketotic insulin-resistant diabetes mellitus. The possibility of malnutrition-related diabetes mellitus was excluded because of (a) no personal or family history of malnutrition (b) no pancreatic calcification (c) total loss of subcutaneous fat and (d) her requirement for insulin was more than 21.2 units/kg body weight which would be too high even for malnutrition-related diabetes mellitus. Attempts were made to control her diabetes initially with subcutaneous boluses insulin, then continuous intravenous insulin infusion (CIVII) and finally orally with fenfluramine and chlorpropamide.

Child↗
PubMed1989

[Partial lipodystrophy and membranoproliferative glomerulonephritis. Apropos of a case].

We have studied a girl seven and a half years old with a renal disease manifested by proteinuria and nephrotic syndrome combined with initial macroscopic hematuria normal blood pressure and persistent depression of the complement C3 levels with the complement activating gamma globulin (C3 Nef) present in serum. The anatomopathological study showed findings of membranoproliferative glomerulonephritis type II with intramembranous deposit (dense deposit disease). An unusual association with partial lipodystrophy was present in this case. A follow-up of five years, and a few considerations about etiopathogenic theories were presented.

Child↗
PubMed1988

Production of C3 nephritic factor by cultured lymphocytes derived from a patient with partial lipodystrophy.

C3 nephritic factor (C3 NeF) has been found mainly in the sera of patients with membranoproliferative glomerulonephritis (MPGN) and partial lipodystrophy (PLD). We examined whether peripheral blood mononuclear cells (PBMC) from a patient with PLD could produce C3 NeF. We investigated the in vitro immunoglobulin synthesis of PBMC with mitogen. We further studied the C3bBb stabilizing activity and undertook agglutination assays of the IgG obtained from the culture supernatants. The patient IgG was able to agglutinate only EAC4b3bBb cells and none of the other intermediate cells. We this demonstrated that C3 NeF could be produced in vitro by PBMC derived from a patient with PLD.

Child↗
PubMed1987

Insulin receptor evaluation in congenital generalized lipodystrophy. Case report of an infant.

Insulin specific receptors on red blood cells and cultured fibroblasts were investigated in a male infant affected of congenital generalized lipodystrophy (CGL). Total insulin binding capacity appeared mildly reduced, with apparently selective involvement of the high-affinity receptors on red blood cells but not on fibroblasts. Such alterations did not produce any impairment of glucose metabolism.

Blood Glucose↗