Insulin resistance in HIV-infected patients: relationship with pro-inflammatory cytokines released by peripheral leukocytes

• Published in: The Journal of infection Vol. 47; no. 1; pp. 52 - 58
• Main Authors: Limone, Paolo, Biglino, Alberto, Valle, Mauro, Degioanni, Maria, Paola Servato, Maria, Berardi, Clara, Del Rizzo, Paola, Pellissetto, Cristina, Carlo Isaia, Giovanni
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-07-2003; Elsevier
• Subjects: Adult; Biological and medical sciences; Blood Glucose - analysis; cytokines; HIV infection; HIV Infections - blood; HIV Infections - physiopathology; Human viral diseases; Humans; Hydrocortisone - blood; Infectious diseases; Insulin - blood; insulin resistance; Insulin Resistance - physiology; Interleukin-1 - blood; Male; Medical sciences; Tumor Necrosis Factor-alpha - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; HIV infection; insulin resistance; cytokines; Infection; Human; Immunopathology; Target tissue resistance; Leukocyte; Pathogenesis; Viral disease; Cytokine; AIDS; Immune deficiency; Insulin
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/S0163-4453(03)00055-0

Objectives. Abnormalities of insulin sensitivity are increasingly reported in HIV infection. Considering that cytokines (particularly TNF-α and IL-1β) can induce insulin resistance in infections, we investigated the relationship between insulin sensitivity and cytokine release from peripheral blood mononuclear cells (PBMCs) in HIV-infected patients.
Methods. Fourteen HIV-positive patients treated with dual-NRTI (nucleosidic reverse transcriptase inhibitors) regimens, and fourteen healthy controls were studied. Insulin resistance was assessed by homeostatic model for insulin resistance (HOMA-IR). Cytokine production by PBMCs ex vivo was measured.
Results. Plasma glucose levels did not differ in HIV patients and in controls. Insulin concentrations and HOMA-IR were significantly higher in HIV-infected patients than in controls (respectively, 11.4±4.3 vs. 7.86±1.1
mIU,
P=0.005; 2.27±0.91 vs. 1.6±0.2,
P=0.025). A significant positive linear correlation was observed between HOMA-IR and TNF-α concentrations in the supernatants of unstimulated PBMC cultures in HIV patients (
r=0.771;
P=0.001
), but not in controls.
Conclusions. Our results are in accordance with previous findings showing that insulin resistance may indeed be present in PI-naive HIV patients, and suggest that either TNF-α, or other mediators released in parallel with this cytokine may induce a state of insulin resistance, unrelated to highly active antiviral treatments, in poorly controlled HIV disease.