Circulating levels of glucoselysine, a fructose-specific glycation product, are modulated by dietary fructose; post-hoc analysis of a case-control study and a randomized controlled trial.
Fructose consumption has been associated with cardiometabolic disease, including type 2 diabetes and cardiovascular disease. The formation of the fructose-specific glycation product glucoselysine (GL) may underlie the development of these complications. A previous study showed that endogenously produced fructose contributes to GL formation.
Here, we aimed to investigate the effects of exogenous fructose on the formation of GL. Methods We first developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) stable isotope dilution method for the quantification of total GL in human serum samples. GL levels were subsequently measured in serum samples obtained from: 1) a case-control study, comparing patients with hereditary fructose intolerance (HFI) (n=15) on a fructose restricted diet with age-, sex- and BMI-matched healthy controls; and 2) a double-blind randomized control trial to study effects of dietary fructose restriction in adults with overweight and hepatic steatosis (n=35).
We successfully developed a UPLC-MS/MS method for the detection of total GL in serum, with inter- and intra-assay variability ranging from 1.1% to 6.0%. Serum GL concentrations were significantly lower in HFI patients compared to healthy controls (35.1 compared with 45.8 nmol/L, difference: -11.5; 95%CI: -14.3, -8.8). Similarly, dietary fructose restriction resulted in significantly lower serum GL levels in individuals with overweight and hepatic steatosis (38.8 pre- compared with 31.2 nmol/L post-intervention, change from baseline: -8.0; 95%CI: -12.0, -4.5).
Total serum GL can be analyzed accurately and precisely using UPLC-MS/MS. Our findings from two clinical studies demonstrate that GL formation is significantly influenced by dietary fructose intake. The observation that GL levels were not completely reduced after dietary fructose restriction suggests that additional factors such as an endogenous fructose pool contribute to GL formation. Further research is needed to elucidate the role of GL formation in fructose-induced cardiometabolic complications.
The FRUITLESS study was registered at https://clinicaltrials.gov/study/NCT03067428, identifier: NCT03067428.
Here, we aimed to investigate the effects of exogenous fructose on the formation of GL. Methods We first developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) stable isotope dilution method for the quantification of total GL in human serum samples. GL levels were subsequently measured in serum samples obtained from: 1) a case-control study, comparing patients with hereditary fructose intolerance (HFI) (n=15) on a fructose restricted diet with age-, sex- and BMI-matched healthy controls; and 2) a double-blind randomized control trial to study effects of dietary fructose restriction in adults with overweight and hepatic steatosis (n=35).
We successfully developed a UPLC-MS/MS method for the detection of total GL in serum, with inter- and intra-assay variability ranging from 1.1% to 6.0%. Serum GL concentrations were significantly lower in HFI patients compared to healthy controls (35.1 compared with 45.8 nmol/L, difference: -11.5; 95%CI: -14.3, -8.8). Similarly, dietary fructose restriction resulted in significantly lower serum GL levels in individuals with overweight and hepatic steatosis (38.8 pre- compared with 31.2 nmol/L post-intervention, change from baseline: -8.0; 95%CI: -12.0, -4.5).
Total serum GL can be analyzed accurately and precisely using UPLC-MS/MS. Our findings from two clinical studies demonstrate that GL formation is significantly influenced by dietary fructose intake. The observation that GL levels were not completely reduced after dietary fructose restriction suggests that additional factors such as an endogenous fructose pool contribute to GL formation. Further research is needed to elucidate the role of GL formation in fructose-induced cardiometabolic complications.
The FRUITLESS study was registered at https://clinicaltrials.gov/study/NCT03067428, identifier: NCT03067428.
Authors
van Oeteren van Oeteren, Simons Simons, van de Waarenburg van de Waarenburg, Houben Houben, Schalkwijk Schalkwijk, Brouwers Brouwers, Scheijen Scheijen
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