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


METHODS
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).


CONCLUSIONS
In HIV+NRTI+ patients, both resting and postexercise levels of lactate were related to insulin resistance rather than mtDNA alterations in skeletal muscle.
Maagaard
Anne
A
Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway. anne.maagaard@medisin.uio.no
Holberg-Petersen
Mona
M
Torjesen
Peter A
PA
Bruun
Johan N
JN
Kvale
Dag
D
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid