Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance

Hyperuricemia is an independent risk factor for the metabolic syndrome and cardiovascular disease. We hypothesized that asymptomatic carriers for hereditary fructose intolerance (OMIM 22960) would have increased uric acid and altered component of the metabolic syndrome when exposed to fructose overfeeding.Six heterozygotes for HFI (hHFI) and 6 controls (Ctrl) were studied in a randomized, controlled, crossover trial. Participants ingested two identical test meals containing 0.7 g kgHiFruD increased fasting uric acid (p 0.05) and reduced fasting insulin sensitivity estimated by the homeostasis model assessment (HOMA) for insulin resistance (p 0.05), in both groups. Postprandial glucose concentrations were not different between hHFI and Ctrl. However HiFruD increased postprandial plasma uric acid, insulin and hepatic insulin resistance index (HIRI) in hHFI only (all p 0.05).Seven days of HiFruD increased fasting uric acid and slightly reduced fasting HOMA index in both groups. In contrast, HiFruD increased postprandial uric acid, insulin concentration and HIRI in hHFI only, suggesting that heterozygosity for pathogenic Aldolase B variants may confer an increased susceptibility to the effects of dietary fructose on uric acid and hepatic insulin sensitivity. This trial was registered at the U.S. Clinical Trials Registry as NCT03545581.