Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients.
Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV-lipodystrophy. These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin concentration were increased (>90%, P < .01) and insulin sensitivity (Log10ISI(composite)) was decreased (-50%, P < .001). Total and free IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease were similar between groups (all P > .5), whereas, in LIPO, IGFBP-1 and IGFBP-2 were reduced (-36%, P < .05 and -50%, P < .01). In pooled groups, total IGF-I, free IGF-I, total IGF-II, and IGFBP-3, respectively, correlated inversely with age (all P < .01). In pooled groups, IGFBP-1 and IGFBP-2 correlated positively with insulin sensitivity (age-adjusted all P < .05). IGFBP-3 protease correlated with free IGF-I in pooled groups (r(p) = 0.47, P < .02), and in LIPO (r(p) = 0.71, P < .007) controlling for age, total IGF-I, and IGFBP-3. GHBP was increased, whereas GH was decreased in LIPO (all P < .05). GH correlated inversely with GHBP in pooled groups (P < .05). Taken together the similar IGFs and IGFBP-3 concentrations between study groups, including suppressed GH, and increased GHBP in LIPO, argue against GH resistance of GH-sensitive tissues in LIPO compared with NONLIPO; however, this notion awaits examination in dose-response studies. Furthermore, our data suggest that IGFBP-3 protease is a significant regulator of bioactive IGF-I in HIV-lipodystrophy.
Haugaard
Steen B
SB
Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Denmark.
Andersen
Ove
O
Hansen
Birgitte R
BR
Orskov
Hans
H
Andersen
Ulrik B
UB
Madsbad
Sten
S
Iversen
Johan
J
Flyvbjerg
Allan
A
D000367:Age Factors; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D010450:Endopeptidases / Q000097:blood / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood* / Q000150:complications; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D016014:Linear Models; D008060:Lipodystrophy / Q000097:blood* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D013002:Somatomedins / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease; C051815:somatotropin-binding protein