Table 2 Summary of NAFLD/NASH clinical trials incorporating stable-label isotope DNL assessments
From: Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease
Subjects | Study Type | Intervention | Period | Tracer | Outcome | Ref |
|---|---|---|---|---|---|---|
Healthy controls (n = NR) | Randomized double-blind, placebo-controlled crossover | Compound 9 (600 mg) or placebo with one week washout | Single dose | [1-13C]-acetate (9–9.5 mg/min) for 20.5 h | Compound 9 reduced fructose-induced fractional DNL | [47] |
Type 2 diabetes (n = 12) | Open label, randomized (1:1) | Pioglitazone (dose escalated to 45 mg/day) Rosiglitazone (dose escalated to 4 mg twice daily) | 20 weeks | [1-13C]-acetate (10 mg/min) For 12 h | Pioglitazone reduced fasting fractional DNL over course of acetate infusion No change with Rosiglitazone | [74] |
Type 2 diabetes (n = 60) | Randomized double-blind placebo-controlled (1:1) | Colesevelam (3.75 g/day) or placebo | 12 weeks | [1-13C]-acetate (10 mg/min) 19.5 h continuous infusion | Placebo increased fasting and postprandial fractional DNL, no change with colesevelam | [81] |
Biopsy-proven NASH (n = 14) | Randomized double-blind, placebo-controlled (1;1) | Liraglutide (dose escalated to 1.8 mg/day) or placebo | 12 weeks | 2H2O (3 g/kg total body water in 2 doses) plus ad libitum drinking water enriched with 0.4 % 2H2O over 20 h | Liraglutide decreased fasting % change DNL | [29] |