Insulin Resistance Is Affected by Increased Levels of Plasma Lactate but not Mitochondrial Alterations in Skeletal Muscle in NRTI- Exposed HIV-Infected Patients

Purpose: To explore the relations between insulin resistance, plasma lactate, and mitochondrial (mt) DNA alterations in skeletal muscle in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors (HIV+NRTI+). Method: Insulin resistance was estimated using the homeostatic model assessment (HOMA-IR). Mitochondrial dysfunction was determined by plasma lactate at rest and after subanaerobic exercise, mitochondrial/nuclear DNA (mt/nDNA) ratio, and mtDNA deletions in skeletal muscle. Results: HIV+NRTI+ patients (n = 27) had higher levels of HOMA-IR, higher lactate at rest as well as after exercise, and more frequent mtDNA deletions and decreased mt/nDNA ratios compared with controls (n = 15). Only in HIV+NRTI+ patients, HOMA-IR correlated with resting lactate (r = 0.5, p = .02) and probably also lactate 3, 5, and 8 minutes after exercise (r = 0.4; p = .075, p = .048, and p = .056, respectively). In contrast, neither HOMA-IR nor the lactate levels correlated with mt/nDNA ratio and mtDNA deletions in skeletal muscle in HIV+NRTI+ patients (r .6), whereas resting lactate correlated with mt/nDNA ratio in HIV seronegative controls (r = –0.7, p = .02). Conclusion: In HIV+NRTI+ patients, both resting and postexercise levels of lactate were related to insulin resistance rather than mtDNA alterations in skeletal muscle. Key words: HIV-1 infection, insulin resistance, lactate, mitochondrial dysfunction