Insulin resistance is affected by increased levels of plasma lactate but not mitochondrial alterations in skeletal muscle in NRTI-exposed HIV-infected patients

HIV Clin Trials. 2007 Sep-Oct;8(5):345-53. doi: 10.1310/hct0805-345.

Abstract

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 < 0.1, p > .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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Humans
  • Insulin Resistance*
  • Lactic Acid / blood*
  • Male
  • Middle Aged
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Muscle, Skeletal / pathology*
  • Reverse Transcriptase Inhibitors / therapeutic use*

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Lactic Acid