title: Markedly diminished lipolysis and partial restoration of glucose metabolism, without changes in fat distribution after extended discontinuation of protease inhibitors in severe lipodystrophic human immunodeficient virus-1-infected patients.
abstract: Treatment for HIV-1 infection is often complicated by a lipodystrophy syndrome associated with insulin resistance and an elevated rate of lipolysis. In eight HIV-1 infected men with lipodystrophy syndrome, we studied the effects of replacement of protease inhibitor (PI) by abacavir on insulin sensitivity and lipolysis by hyperinsulinemic euglycemic clamp and on fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan. Glucose metabolism and lipolysis were assessed by tracer dilution employing [6,6-(2)H(2)]glucose and [(2)H(5)]glycerol, respectively. Data are expressed as mean +/- sd or 95% confidence interval (CI), as appropriate. There were no significant changes in fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan at wk 36 and wk 96. The fasting total glucose production decreased from 16.1 +/- 2.5 at study entry by 1.1 (range, -2.1 to -0.1) to 15.0 +/- 1.5 micromol/kg.min after PI withdrawal at wk 36 (n = 8). In an analysis restricted to the patients on treatment at wk 96 (n = 6), the decrease was 0.9 (range, -2.1 to 0.3) micromol/kg.min. During insulin infusion, glucose oxidation (as percent of total glucose disposal) increased from 36.8 +/- 12.7% by 11.0% (range, 1.3-20.8) to 47.9 +/- 13.9% in the wk 36 analysis. In the analysis restricted to the patients on treatment at wk 96 (n = 6) the increase was 7.7 (-4.0 to 19.4)%. Fasting lipolysis decreased from 2.7 +/- 0.6 micromol/kg.min by 0.9 (-1.6 to -0.2) to 1.8 +/- 0.3 micromol/kg.min in the wk-96 analysis (n = 6). The replacement of the studied PIs by abacavir in severe lipodystrophic HIV-1-infected patients results in a marked reduction of lipolysis. In contrast, fasting glucose production and insulin-stimulated glucose oxidation improve moderately, whereas insulin-stimulated glucose disposal and fat distribution do not change.
authors.affiliation: International Antiviral Therapy Evaluation Center, Academic Medical Center, T0-120, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.vandervalk@amc.uva.nl
authors.forename: Marc
authors.initials: M
authors.lastname: van der Valk
authors.forename: Gideon
authors.initials: G
authors.lastname: Allick
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Kuijk
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Hans P
authors.initials: HP
authors.lastname: Sauerwein
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage*; D019233:Retreatment; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D005947:Glucose; D005990:Glycerol; D011480:Protease Inhibitors; D000099227:Abacavir