Isocaloric Fructose Restriction Reduces Serum D-Lactate Concentration in Children With Obesity and Metabolic Syndrome.

Author(s): Erkin-Cakmak, Ayca; Bains, Yasmin; Caccavello, Russell; Noworolski, Susan M; Schwarz, Jean-Marc; Mulligan, Kathleen; Lustig, Robert H; Gugliucci, Alejandro | Abstract: OBJECTIVE:To investigate the link between dietary sugar consumption and two separate pathogenetic mechanisms associated with metabolic syndrome: de novo lipogenesis (DNL) and non-enzymatic glycation. DESIGN AND PARTICIPANTS:We assessed changes in serum D-lactate (the detoxification end-product of methylglyoxal) concentration in response to nine days of isocaloric fructose restriction in 20 children with obesity and metabolic syndrome, and examined correlations with changes in DNL, liver fat, insulin sensitivity and other metrics of hepatic metabolism. INTERVENTIONS:Nine days of dietary sugar restriction, with substitution of equal amounts of refined starch. MAIN OUTCOME MEASURES:On day 0 and 10, children had lab evaluation of D-lactate levels and other analytes, and underwent oral glucose tolerance testing, magnetic resonance spectroscopy to quantify fat depots, and 13C-acetate incorporation into triglyceride to measure DNL. RESULTS:D-lactate was associated with baseline liver fat fraction (pl0.001) and visceral adipose tissue (pl0.001), but not with subcutaneous adipose tissue. At baseline, D-lactate was positively correlated with DNL-AUC (p=0.003), liver fat fraction (p=0.02), triglyceride (p=0.004) and triglyceride to HDL ratio (p=0.002). After nine days of isocaloric fructose restriction, serum D-lactate levels reduced by 50% (pl0.0001), and changes in D-lactate correlated with both changes in DNL-AUC, and measures of insulin sensitivity. CONCLUSION:Baseline correlation of D-lactate with DNL and measures of insulin sensitivity; and reduction in D-lactate following nine days of isocaloric fructose restriction suggest that DNL and non-enzymatic glycation are functionally linked via intermediary glycolysis in the pathogenesis of metabolic syndrome, and points to fructose as a key dietary substrate that drives both pathways.