Insulin Resistance in HIV-infected Patients: Relationship with Pro-inflammatory Cytokines Released by Peripheral Leukocytes

Objectives: Abnormalities of insulin sensitivity are increasingly reported in HIV infection. Considering that cytokines (particularly TNF-alpha and IL-1beta) 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+/-1.1mIU, 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-alpha 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-alpha, 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.