Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in beta-cell function.
The pathophysiology of insulin resistance in human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is not fully clarified. We investigated 18 men with HALS and 18 HIV-positive males without lipodystrophy (control subjects). Duration and modality of antiretroviral therapy were similar between study groups. A hyperinsulinemic euglycemic clamp showed an impaired glucose disposal rate (GDR) in HALS patients (5.6 v 8.3 mg glucose/min. kg(FFM), P =.0006). As demonstrated by indirect calorimetry, HALS patients showed an impaired nonoxidative glucose metabolism (NOGM, 2.2 v 4.2, P =.006), whereas levels of basal and insulin-stimulated oxidative glucose metabolism (OGM) (2.4 v 2.3, P =.55, and 3.3 v 4.0, P =.064, respectively) were not significantly different between groups. Despite comparable total fat masses, dual energy x-ray absorptiometry (DEXA) scans showed that the percentage of limb fat (ie, peripheral-fat-mass/[peripheral-fat-mass + trunk-fat-mass]. 100%) was reduced in HALS patients (36% v 46%, P =.0002). Multiple linear regression analysis indicated that percentage of limb fat explained 53% of the variability of GDR and 45% of the variability of NOGM in HALS patients. In HALS patients, leg fat mass correlated positively with NOGM (r =.51, P <.05), whereas abdominal fat mass and NOGM did not correlate (P =.91). Analyzing the relationship between first phase insulin secretion and insulin sensitivity, 6 HALS patients compared with none of the control subjects exhibited impaired insulin secretion (P <.05). Our data suggest that fat redistribution independently of antiretroviral therapy is highly related to insulin resistance in HALS patients. Furthermore, in HALS patients, impaired glucose metabolism most likely relates to decreased NOGM and to defects in beta-cell function.
Andersen
Ove
O
Department of Infectious Diseases, Internal Medicine and Endocrinology and Clinical Psysiology, Hvidovre University Hospital, Copenhagen, Denmark.
Haugaard
Steen B
SB
Andersen
Ulrik B
UB
Friis-Møller
Nina
N
Storgaard
Heidi
H
Vølund
Aage
A
Nielsen
Jens Ole
JO
Iversen
Johan
J
Madsbad
Sten
S
D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D000328:Adult; D001823:Body Composition; D002153:Calorimetry, Indirect; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male
D007328:Insulin