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Divisions of 4 Infectious Diseases, 5 Diagnostic Radiology, and 6 Nuclear Medicine, 2 Clinical Research Unit II, and 3 Clinical Spectroscopy Unit, San Raffaele Scientific Institute, and 1 International Center for Assessment of the Nutritional Status, Universita' degli Studi di Milano, 20132 Milan, Italy
Antiretroviral therapy in
human immunodeficiency virus (HIV)-positive patients can induce a
lipodystrophy syndrome of peripheral fat wasting and central adiposity,
dyslipidemia, and insulin resistance. To test whether in this syndrome
insulin resistance is associated with abnormal muscle handling of fatty
acids, 12 HIV-1 patients (8 females/4 males , age = 26 ± 2 yr, HIV duration = 8 ± 1 yr, body mass index = 22.0 ± 1.0 kg/m2, on protease inhibitors and
nucleoside analog RT inhibitors) and 12 healthy subjects were studied.
HIV-1 patients had a total body fat content (assessed by dual-energy
X-ray absorptiometry) similar to that of controls (22 ± 1 vs.
23 ± 2%; P = 0.56), with a topographic fat
redistribution characterized by reduced fat content in the legs
(18 ± 2 vs. 32 ± 3%; P < 0.01) and
increased fat content in the trunk (25 ± 2 vs. 19 ± 2%;
P = 0.03). In HIV-positive patients, insulin
sensitivity (assessed by QUICKI) was markedly impaired (0.341 ± 0.011 vs. 0.376 ± 0.007; P = 0.012). HIV-positive patients also had increased total plasma cholesterol (216 ± 20 vs. 174 ± 9 mg/dl; P = 0.05) and triglyceride
(298 ± 96 vs. 87 ± 11 mg/dl; P = 0.03)
concentrations. Muscular triglyceride content assessed by means of
1H NMR spectroscopy was higher in HIV patients in soleus
[92 ± 12 vs. 42 ± 5 arbitrary units (AU);
P < 0.01] and tibialis anterior (26 ± 6 vs.
11 ± 3 AU; P = 0.04) muscles; in a stepwise
regression analysis, it was strongly associated with QUICKI
(R2 = 0.27; P < 0.0093).
Even if the basal metabolic rate (assessed by indirect calorimetry) was
comparable to that of normal subjects, postabsorptive lipid oxidation
was significantly impaired (0.30 ± 0.07 vs. 0.88 ± 0.09 mg · kg
1 · min1;
P < 0.01). In conclusion, lipodystrophy in HIV-1
patients in antiretroviral treatment is associated with intramuscular
fat accumulation, which may mediate the development of the insulin resistance syndrome.
human immunodeficiency virus
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