Glucose Production Pathways by ²H and ¹³C NMR in Patients with HIV-Associated Lipoatrophy

Patients with HIV taking protease inhibitors were selected for the presence (five subjects) or absence (five subjects) of lipoatrophy. Following an overnight fast, subjects were given oral ²H₂O in divided doses (5 mL/kg body water), [U-¹³C₃] propionate (10 mg/kg), and acetaminophen (1000 mg). Glucose (from plasma) or acetaminophen glucuronide (from urine) were converted to mono-acetone glucose for ²H NMR and ¹³C NMR analysis. The fraction of plasma glucose derived from gluconeogenesis was not significantly different between groups. However, flux from glycerol into gluconeogenesis relative to glucose production was increased from 0.20 ± 0.13 among subjects without lipoatrophy to 0.42 ± 0.12 (P < 0.05) among subjects with lipoatrophy, and the TCA cycle contribution was reduced. Lipoatrophy was associated with an abnormal profile of glucose production as assessed by ¹³C and ²H NMR of plasma and urine.