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PubMed2004

Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome).

The lipodystrophies are a heterogeneous group of disorders of adipose tissue associated with insulin resistance. The sporadic form of partial lipodystrophy, characterised by fat loss from the face and upper body, is associated with complement abnormalities and mesangiocapillary glomerulonephritis type 2 (MCGN II) and the conditions are thought to have a shared autoimmune aetiology. We present the first case of the rare familial form of partial lipodystrophy, caused by a mutation in the LMNA gene, associated with MCGN II. This suggests that partial lipodystrophy of both the sporadic and familial subtypes may predispose to this condition and that the observed renal and complement abnormalities may be secondary to other factors associated with lipodystrophy.

Adult↗
PubMed2002

Highly active antiretroviral therapy-induced lipodystrophy has minor effects on human immunodeficiency virus-induced changes in lipolysis, but normalizes resting energy expenditure.

Combination antiretroviral therapy for the treatment of human immunodeficiency virus type 1-infected patients is associated with development of the lipodystrophy syndrome (LD). We previously showed that plasma levels of free fatty acids are higher in patients with lipodystrophy. The purpose of this study was to evaluate the postabsorptive rate of lipolysis, using [(2)H(5)]glycerol infusion, the resting energy expenditure (REE) measured by indirect calorimetry, and the responses of both to epinephrine infusion ( approximately 15 ng/kg.min) in patients with LD. Results were compared with those obtained in five matched human immunodeficiency virus type 1-infected patients. The postabsorptive rate of appearance of glycerol did not differ between the two groups. There was no difference in the lipolytic response to epinephrine, although the response in the LD group was delayed (P < 0.001). The postabsorptive REE adjusted for lean body mass was lower and remained lower during epinephrine infusion in the LD group. Postabsorptive norepinephrine concentrations were higher and remained elevated during epinephrine infusion in the LD group. We conclude that the lipolytic response to epinephrine in the LD group was normal, albeit delayed. Norepinephrine concentrations were increased in patients with lipodystrophy, indicating increased sympathetic activity. Postabsorptive REE was lower in the patients with lipodystrophy. Our data suggest that highly active antiretroviral therapy-associated lipodystrophy normalizes the REE, but has only minor effects on lipolysis as a result of concomitant sympathetic stimulation of adipose tissue.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.

Mandibuloacral dysplasia (MAD) is a phenotypically heterogeneous, rare autosomal recessive disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, joint contractures, and mottled cutaneous pigmentation. Patients with MAD develop two patterns of lipodystrophy: type A pattern, with loss of sc fat from the extremities and normal or slight excess in the neck and truncal regions; and type B pattern, with a more generalized loss of sc fat involving the face, trunk, and extremities. Recently, affected patients from five consanguineous Italian pedigrees with partial lipodystrophy (type A) were reported to have a homozygous R527H mutation in LMNA (lamin A/C) gene. We carried out mutational analysis of LMNA in affected patients from six pedigrees. Affected patients from two pedigrees with type A lipodystrophy had the homozygous R527H mutation in LMNA. The other four affected subjects who had type B lipodystrophy did not have any mutation in the exons and splice site junctions of LMNA; RNA extracted from lymphoblasts of two of these patients also revealed normal sequence. In these four subjects, sequencing of other known genes implicated in lipodystrophies, i.e. AGPAT2, Seipin, and PPARG also revealed no substantial alterations. We conclude that MAD is a genetically and phenotypically heterogeneous disorder. Besides LMNA gene, other as yet unmapped loci could be linked to MAD.

Adolescent↗
PubMed1999

Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy.

Multidrug antiretroviral regimens that include human immunodeficiency virus-1 (HIV-1) protease inhibitors are associated with distinct lipodystrophy, hypertriglyceridemia, hyperinsulinemia, and deposition of visceral abdominal adipose tissue. To determine whether these findings are related to abnormalities of adrenal function, we compared the hypothalamic-pituitary-adrenal axes of HIV-positive patients who had evidence of protease inhibitor-associated lipodystrophy (PIAL), control volunteers (CON), and patients with Cushing's syndrome (CS). To elucidate the metabolic consequences of the observed lipodystrophy, we measured basal serum lipids and compared glucose and insulin concentrations during an oral glucose tolerance test. Spontaneous plasma cortisol showed normal diurnal variation in PIAL. Cortisol levels were similar in CON and PIAL, and levels in these groups were less than those in CS at all times of the night or day (P < 0.005). Ovine CRH-stimulated morning plasma cortisol levels were similar in PIAL and CON. ACTH was significantly greater in PIAL than CON (P < 0.05) at 0, 15, and 30 min after CRH stimulation. Urinary free cortisol in PIAL (mean +/- SD, 76 +/- 51 nmol/day) was significant lower than those in CON (165 +/- 64 nmol/day; P < 0.001) and CS (1715 +/- 1203 nmol/day; P < 0.001). However, 17-hydroxycorticosteroid excretion was significantly greater in PIAL (43 +/- 23 micromol/day) than in CON (17 +/- 8 micromol/day; P < 0.001), although lower than that in CS (74 +/- 47 micromol/day; P < 0.01). Scatchard analysis revealed normal glucocorticoid receptor number and affinity in PIAL. Serum triglycerides were significantly greater in PIAL (6.57 +/- 5.63 mmol/L) than in CS (1.78 +/- 0.83 mmol/L; P < 0.001) or CON (1.36 +/- 0.84 mmol/L; P < 0.001). Although triglyceride levels were significantly correlated with body mass index for CON and CS, these were not correlated for PIAL. During an oral glucose tolerance test, similar glucose and insulin values were found in PIAL and CS that were greater (P < 0.05) than CON values at 30, 60, 90, and 120 min. We conclude that the lipodystrophy associated with use of HIV-1 protease inhibitors is a syndrome of increased intraabdominal adiposity with concomitant dyslipidemia and insulin resistance, but without total body weight gain and is distinct from any known form of hypercortisolism. Although urinary cortisol disposition seems to be altered in HIV-infected patients who are being treated with multidrug regimens that include protease inhibitors, the decreased free cortisol and increased 17-hydroxycorticosteroid excretion appear to be unlikely explanations for the observed lipodystrophy. The cause remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed2001

Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy.

Human immunodeficiency virus (HIV) lipodystrophy (LIPO) is characterized by increased visceral adiposity, peripheral fat atrophy, dyslipidemia, and insulin resistance. GH concentrations are known to vary inversely with excess weight and body fat but have not been investigated in HIV lipodystrophy. Twenty-one subjects with HIV LIPO, 20 HIV-infected nonlipodystrophy subjects (NONLIPO), and 20 control (C) subjects were prospectively recruited for this study and compared. Subjects in the three groups were all male, age-matched [median, 47 yr old (interquartile range, 37-50) LIPO; 41 (37-44) NONLIPO; and 43 (37-49) C], and body mass index-matched [median, 24.3 kg/m(2) (interquartile range, 22.2-26.6) LIPO; 24.4 (23.3-25.9) NONLIPO; and 24.8 (22.7-26.1) C] (P: > 0.05 for all comparisons). Visceral abdominal fat [16,124 mm(2) (11,246-19,790) LIPO; 7,559 (5,134-11,201) NONLIPO; and 8,803 (6,165-11,623) C; P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] and the ratio of visceral abdominal fat to sc abdominal fat [1.37 (0.71-2.44) LIPO vs. 0.57 (0.47-0.78) NONLIPO vs. 0.55 (0.41-0.71) C, P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] were significantly increased in the LIPO subjects but were not significantly different between NONLIPO and C. The mean overnight GH concentration, determined from frequent sampling every 20 min (from 2000 h to 0800 h) was decreased in the LIPO subjects [0.38 microg/L (0.13-0.67) LIPO vs. 0.96 (0.53-1.30) NONLIPO vs. 0.81 (0.49-1.03) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and not significantly different between NONLIPO and C. Pulse analysis demonstrated decreased baseline GH [0.08 microg/L (0.06-0.21) LIPO vs. 0.19 (0.10-0.32) NONLIPO vs. 0.17 (0.12-0.57) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and GH peak amplitude [1.06 microg/L (0.46-1.94) LIPO vs. 2.47 (1.22-3.43) NONLIPO and 2.27 (1.36-4.25) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] in the LIPO subjects but no significant difference in pulse frequency. No significant differences were observed between NONLIPO and C for any GH parameter. Insulin-like growth factor-I was not different between the groups. Total body fat (r = -0.40, P = 0.01) and visceral fat (r = -0.58, P = 0.0001) correlated inversely with mean overnight GH concentrations in the HIV-infected patients. In a multivariate regression model, controlling for age, body mass index, body fat, and visceral fat, only visceral fat was a significant predictor of mean GH concentrations (P = 0.0036, r(2) for model = 0.40). These data demonstrate normal GH pulse frequency and insulin-like growth factor-I concentrations but reduced mean GH concentrations, basal GH concentrations, and GH pulse amplitude in patients with HIV lipodystrophy. Increased visceral adiposity is the strongest predictor of reduced GH concentrations in HIV lipodystrophy. Further studies are necessary to determine the clinical significance of reduced GH in patients with HIV lipodystrophy.

Abdomen↗
PubMed2005

GH treatment reduces trunkal adiposity in HIV-infected patients with lipodystrophy: a randomized placebo-controlled study.

OBJECTIVE: HIV lipodystrophy is a common complication of highly active anti-retroviral therapy, characterized by both metabolic and morphological features. The most feared morphological feature is body fat redistribution leading to HIV lipodystrophy. GH is known to induce reduction of visceral obesity and body fat redistribution in adults. DESIGN: A crossover, double-blind protocol of GH treatment (6 months of recombinant human GH (rhGH) at 0.2 IU/kg per week) vs placebo (6 months of placebo with a 2 month wash-out between periods) was performed. SUBJECTS AND SETTING: Thirty HIV-infected patients with lipodystrophy were recruited in the Outpatient Clinic of the Division of Infectious Diseases of San Raffaele Scientific Institute in Milan, Italy. MAIN OUTCOME AND RESULTS: Our data demonstrate an effect of low-dose rhGH administration in reducing trunk adiposity in HIV patients with lipodystrophy (Delta from basal: -394 +/- 814 g, P = 0.048 with respect to placebo. Data are given as mean +/- standard deviation). A trend to an increase of arm depots was also shown (Delta from basal: +43 +/- 384 g, P = NS with respect to placebo). Interestingly, no detrimental metabolic effects on glucose tolerance and lipid levels were found following the administration of 0.2 IU/kg per week of rhGH for 6 months. CONCLUSIONS: Low-dose GH administration is an effective treatment in reducing trunk obesity in HIV-infected patients with lipodystrophy.

Abdominal Fat↗
PubMed2001

Lipodystrophy syndrome in patients with HIV infection: quality of life issues.

Current antiretroviral therapy has lead to longer survival in patients infected with HIV, but it is also associated with new and important problems. Body fat redistribution and metabolic abnormalities, the so-called lipodystrophy syndrome, are among the most prevalent and worrisome ones. While an increasing number of patients infected with HIV are becoming affected by this syndrome, the pathogenesis of this syndrome and how to prevent and treat the problem all remain largely unknown. Body fat changes stigmatise the bodies of patients infected with HIV giving them a similar look to that seen in patients some years ago when the wasting syndrome was more prevalent and HIV infection was ultimately fatal. The psychological impact of body fat changes may be severe enough to affect a patients' desire to continue with antiretroviral therapy. Metabolic abnormalities, probably with the exception of symptomatic diabetes mellitus and hypertriglyceridaemia-induced pancreatitis, do not have an immediate impact on the quality of the lives of patients with HIV. However, their potential long term cardiovascular and bone consequences may increase the morbidity and the mortality of patients infected with HIV through noninfectious diseases. The impact of lipodystrophy on patients infected with HIV is not readily captured with the classic instruments used to measure quality of life and hence it is necessary to modify them urgently. Though treating lipodystrophy seems fully justified, there is no proven treatment for this problem, although a number of treatments have been used with varying success. Despite the recognition that lipodystrophy may have important psychological repercussions, the best psychological approach for this problem is not known at present. Although lipodystrophy has its own peculiarities, existing knowledge about how to psychologically help other patients with deforming body changes might be of help for patients infected with HIV, or at least may act as a starting point.

Antiretroviral Therapy, Highly Active↗
PubMed2002

PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy.

Autosomal dominant familial partial lipodystrophy (FPLD) due to mutant LMNA encoding nuclear lamin A/C is characterized by adipose tissue repartitioning together with multiple metabolic disturbances, including insulin resistance and dyslipidemia. There is emerging evidence that some rare mutations in peroxisome proliferator-activated receptor-gamma (PPAR-gamma), encoded by PPARG, might be associated with human lipodystrophy. We report a three-generation Canadian kindred ascertained based upon partial lipodystrophy, with a normal LMNA gene sequence. Candidate gene sequencing showed that all four affected subjects were heterozygous for a novel T-->A mutation at PPARG nucleotide 1164 in exon 5 that predicted substitution of phenylalanine at codon 388 by leucine (F388L). The mutation was absent from normal family members and normal unrelated subjects, and altered a highly conserved residue within helix 8 of the predicted ligand-binding pocket of PPAR-gamma. The mutant receptor had significantly decreased basal transcriptional activity and impaired stimulation by a synthetic ligand. The germline transmission of a transactivation-deficient mutation in PPARG suggests that autosomal dominant partial lipodystrophy is genetically heterogeneous. Our findings are consistent with the idea that mutant PPARG can underlie the partial lipodystrophy phenotype.

Adult↗
PubMed2005

Long-term efficacy of leptin replacement in patients with generalized lipodystrophy.

Ectopic fat accumulation has been implicated as a contributing factor in the abnormal metabolic state of obesity. One human model of ectopic fat deposition is generalized lipodystrophy. Generalized lipodystrophy is a rare disorder characterized by a profound deficiency of adipose tissue with resultant loss of triglyceride storage capacity and reduced adipokines, including leptin. Subjects with generalized lipodystrophy and reduced leptin levels often have an increased appetite leading to hyperphagia. Excess fuel consumption, coupled with a lack of adipose tissue, contributes to the significant ectopic triglyceride accumulation in the muscle and liver seen in these subjects. This ectopic fat, along with the deficiency in leptin signaling and perhaps other adipokines, likely contributes to insulin resistance, diabetes, and hepatic steatosis. We report here the long-term effects of leptin replacement in a cohort of these subjects. Fifteen patients with generalized lipodystrophy were treated with twice-daily recombinant methionyl human leptin (r-metHuLeptin) for 12 months. We evaluated metabolic parameters at baseline and every 4 months. Antidiabetes medications were decreased or discontinued as necessary. Reductions were seen in serum fasting glucose (from 205 +/- 19 to 126 +/- 11 mg/dl; P < 0.001), HbA1c (from 9 +/- 0.4 to 7.1 +/- 0.5%; P < 0.001), triglycerides (from 1,380 +/- 500 to 516 +/- 236 mg/dl; P < 0.001), LDL (from 139 +/- 16 to 85 +/- 7 mg/dl; P < 0.01), and total cholesterol (from 284 +/- 40 to 167 +/- 21 mg/dl; P < 0.01). HDL was unchanged (from 31 +/- 3 to 29 +/- 2 mg/dl; P = 0.9). Liver volumes were significantly reduced (from 3,663 +/- 326 to 2,190 +/- 159 cm3; P < 0.001), representing loss of steatosis. Decreases were seen in total body weight (from 61.8 +/- 3.6 to 57.4 +/- 3.4 kg; P = 0.02) and resting energy expenditure (from 1,929 +/- 86 to 1,611 +/- 101 kcal/24 h; P < 0.001). R-metHuLeptin led to significant and sustained improvements in glycemia, dyslipidemia, and hepatic steatosis. Leptin represents the first novel, effective, long-term treatment for severe forms of lipodystrophy.

Adolescent↗
PubMed2002

Evaluation of the risk factors associated with lipodystrophy development in a cohort of HIV-positive patients.

The prevalence of lipodystrophy in an HIV-infected population and the risk factors associated with body shape changes were analysed in this study. Five hundred and four subjects were included. Among these, 201 (39.9%) had features of lipodystrophy syndrome (cases); 303 (60.1%) constituted the control group. Compared with the control group, the lipodystrophy subjects were different in age (P = 0.01); duration of antiretroviral therapy (P < 0.001); length of exposure to nucleoside reverse transcriptase inhibitors (NRTIs) (P < 0.001) and to protease inhibitors (P < 0.001); nadir of CD4 cell count (P < 0.001); and value of plasma HIV-RNA before antiretroviral therapy (P = 0.008). In a multivariate analysis, length of therapy and a nadir CD4 cell count below 250 cell/microl were associated with an increased risk of lipodystrophy. Among patients with lipodystrophy, isolated fat loss was observed in 46 (23%); isolated fat accumulation in 40 (20%); mixed (loss and accumulation) syndrome in 50 (25%); and isolated metabolic changes in 65 (32%). Subjects with morphological alterations displayed a greater cumulative time of exposure to NRTIs and to protease inhibitors than patients with isolated metabolic alterations. Patients with lipoatrophy had had a greater exposure to stavudine.

Adolescent↗
PubMed1984

[Partial lipodystrophy syndrome (Dunnigan type)].

Special forms of partial lipodystrophy, which in contrast to the progressive lipodystrophy of Barraquer-Simons spare the face, have been reported by Dunnigan and Köbberling. Lipodystrophy of the Dunnigan type affects the trunk and limbs; in lipodystrophy of the Köbberling type the loss of subcutaneous fat is restricted to the extremities. The following case report deals with the main clinical and laboratory findings in lipodystrophy of the Dunnigan type.

Acanthosis Nigricans↗
PubMed2005

Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia.

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.

Adult↗
PubMed2001

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Adult↗
PubMed2005

Lipodystrophy and serum lipid abnormalities in HIV-positive sub-Saharan population on ART.

To evaluate whether racial factors may be involved in the development of ART-induced lipodystrophy and/or lipid serum abnormalities, we carried-out a case-control study on all 23 consecutive anti-HIV-positive sub-Saharan black African patients observed from September 20fc01 to December 2001 ('Cases') and 23 Caucasian 'Controls' pair-matched for sex, age (+/-5 years), number of CD4 cells (+/-100 cells), clinical stage of HIV infection, overall duration (+/-3 months) of anti-retroviral treatment and type and duration (+/-3 months) of the last anti-retroviral regimen. The cases, as compared with the controls, less frequently showed lipodystrophy (4.4 vs. 65.2%, P<0.001) and hypertriglyceridemia (8.8 vs. 56.5%, P<0.005), whereas the prevalence of subjects with hypercholesterolemia was similar in the two groups (30 and 39.1%, respectively). Overall, the prevalence of patients lacking both lipodystrophy and serum lipid abnormalities was markedly higher for the cases than for the controls (69.5 vs. 13%, P<0.001). This study seems to indicate that anti-retroviral-induced lipodystrophy and hypertriglyceridemia may be associated to some racial factor.

Adult↗
PubMed2005

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance.

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic, human immunodeficiency virus (HIV)-infected patients with and without lipodystrophy. We studied 18 HIV-infected patients with lipodystrophy (LIPO) on antiretroviral therapy and 25 HIV-infected patients without lipodystrophy (controls) of whom 18 were on antiretroviral therapy and 7 were not. Posthepatic insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting insulin (130%, P < .001), impaired insulin sensitivity index (M value, -29%, P < .001), and reduced MCRi (-17%, P < .01). Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P < .02 and r = -0.68, P < .002) and positively with M value (r = 0.63, P < .01 and r = 0.65, P < .004). In controls, MCRi correlated inversely with fasting insulin (r = -0.47, P < .02) and positively with M value (r = 0.57, P < .004); however, the correlations between HEXi and these parameters were insignificant (P > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy.

Adipose Tissue↗
PubMed1994

Membranous lipodystrophy: secondary type.

BACKGROUND: A peculiar type of fat necrosis was noted in some patients with various skin diseases. OBJECTIVE: We attempted to develop a classification of membranous lipodystrophy combining the results of our study and a review of other articles. METHODS: Five cases of skin diseases with membranous lipodystrophy were studied and their clinical and histopathologic features were analyzed. Previous reports of similar findings were reviewed. RESULTS: Membranous lipodystrophic changes were noted in morphea profunda, lupus panniculitis, and factitial ulcer. Microcysts were formed by the coalescence of the destroyed fat cells and were lined by amorphous, eosinophilic material. Some of the linings had a crenelated appearance. Microgranules were found in the histiocytes and in the hyalinized collagen stroma. The linings and microgranules stained positively with periodic acid-Schiff, were resistant to diastase, and also stained with Sudan black B. CONCLUSION: We propose the use of the term secondary membranous lipodystrophy to describe the local subcutaneous membranous lipodystrophic change that occurs as a result of other skin diseases, in contrast to primary idiopathic membranous lipodystrophy, which occurs without any antecedent factors.

Adipose Tissue↗
PubMed2005

[Antiretroviral treatments-related lipodystrophy syndrome: clinico-pathological findings].

Effective therapies are available that can stop or slow down the progression of HIV infection. Highly active antiretroviral therapy (HAART) is a combination of antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors. Among the side effects due to these drugs, lipodystrophy is a pathology characterized by fat wasting in face and limbs, accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia (hypertriglyceridemia and hypercholesterolemia), insulin resistance, and lactic acidemia. The main clinical features include peripheral fat loss (presumed lipoatrophy in the face, limbs, and buttocks) and central fat accumulation (within the abdomen, breasts, and over the dorsocervical spine, so-called "buffalo hump"). Histopathological features disclose a peculiar type of involutional lipodystrophy. Skin biopsies generally show thinning of the subcutaneous fat, associated with fibrosis, lipogranuloma and sometimes vessel proliferation. There is still an open debate concerning the precise responsibility of HAART as well as the metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. There is no proven therapy for any component of lipodystrophy syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Lipodystrophy associated with protease inhibitors.

Lipodystrophies, characterized by reduction of subcutaneous fat over part or all of the body surface, are uncommon. Their causes are unknown. Recently, lipodystrophy has been reported in human immunodeficiency virus (HIV)-infected patients taking protease inhibitors, which have been recommended since 1996 as standard therapy for HIV disease in combination with nucleoside analogues. In these cases, lipodystrophy consists of an association of peripheral lipoatrophy with central adiposity. We report four HIV-infected men on protease inhibitors who developed a disfiguring lipodystrophy. In three of them, the protease inhibitor was administered for a mean duration of 21.5 months (range 19-23) with good immunological and virological responses. Patient 4 had been treated for 2 years with successive combinations of protease inhibitors with nucleoside analogues without success. The four patients progressively developed an increase in abdominal girth associated with fat wasting of the face and legs. Two of them had recurrent paronychia of the great toes. Triglyceride levels were moderately increased in all patients, and one had a slightly increased cholesterol level. One patient had elevated glucose and insulin plasma levels during a glucose tolerance test. In two patients, a deep biopsy taken from the thigh showed thinning of the subcutaneous fat without other morphological changes. Computed tomographic scans of the face and abdomen confirmed the loss of almost all subcutaneous fat of the cheek and temporal regions, and abdominal perivisceral fat accumulation. For patients 1-3, the protease inhibitor was replaced by a non-nucleoside reverse transcriptase inhibitor. Nine months later, dysmorphic changes had not regressed, but lipid abnormalities had returned to normal and the paronychia had disappeared.

Acquired Immunodeficiency Syndrome↗