The complex human urinary sugar profile: determinants revealed in the cross-sectional KarMeN study

Abstract

BackgroundAlthough sugars and sugar derivatives are an important class of metabolites involved in many physiologic processes, there is limited knowledge on their occurrence and pattern in biofluids.ObjectiveOur aim was to obtain a comprehensive urinary sugar profile of healthy participants and to demonstrate the wide applicability and usefulness of this sugar profiling approach for nutritional as well as clinical studies.DesignIn the cross-sectional KarMeN study, the 24-h urine samples of 301 healthy participants on an unrestricted diet, assessed via a 24-h recall, were analyzed by a newly developed semitargeted gas chromatography–mass spectrometry (GC-MS) profiling method that enables the detection of known and unknown sugar compounds. Statistical analyses were performed with respect to associations of sex and diet with the urinary sugar profile.ResultsIn total, 40 known and 15 unknown sugar compounds were detected in human urine, ranging from mono- and disaccharides, polyols, and sugar acids to currently unknown sugar-like compounds. A number of rarely analyzed sugars were found in urine samples. Maltose was found in statistically higher concentrations in the urine of women compared with men and was also associated with menopausal status. Further, a number of individual sugar compounds associated with the consumption of specific foods, such as avocado, or food groups, such as alcoholic beverages and dairy products, were identified.ConclusionsWe here provide data on the complex nature of the sugar profile in human urine, of which some compounds may have the potential to serve as dietary markers or early disease biomarkers. Thus, comprehensive urinary sugar profiling not only has the potential to increase our knowledge of host sugar metabolism, but can also reveal new dietary markers after consumption of individual food items, and may lead to the identification of early disease biomarkers in the future. The KarMeN study was registered at drks.de as DRKS00004890.

Exploring the Diversity of Sugar Compounds in Healthy, Prediabetic, and Diabetic Volunteers

“…The 40 different sugar and sugar‐like compounds we detected in human plasma were almost all recently identified by us as normal constituents of human urine. [ 19 ] This is an important finding with respect to large cohort studies, where often only plasma samples are available; meaning plasma sugar compounds are similar to 24 h urine samples, although concentrations in plasma are generally lower. In volunteers with IR or type 2 diabetes numerous sugar compounds show characteristic plasma profiles that mimic those of glucose, with rapid clearance during the OGTT in healthy individuals, but not in an IR or diabetic state.…”

“…[ 42 ] We here demonstrate the appearance of lactulose from the test drink (assessment of oral‐cecal transit time) in peripheral blood. We also detected lactose, which in urine has been described as candidate marker for dairy consumption [ 19,43 ] and similarly, sucrose in urine was proposed as a marker for total dietary sugar intake. [ 44 ] The origin of the other detected disaccharides is currently a mystery.…”

“…We recently established a semitargeted sugar profiling method and demonstrated a rather complex mixture comprising 55 different sugar compounds in urine samples of healthy human volunteers. [ 19 ] This finding suggested that the plasma sugar profile is equally complex. Metabolite profiling studies of human biofluids typically analyze only a few sugar compounds; this is mainly due to analytical limitations such as insufficient separation and identification of structural isomers.…”

“…Metabolite profiling studies of human biofluids typically analyze only a few sugar compounds; this is mainly due to analytical limitations such as insufficient separation and identification of structural isomers. [ 19–22 ] Therefore, sugars or sugar‐like candidates are often reported as unknowns, [ 8,14 ] or are represented as a group, for example “hexoses” [ 7,9,14 ] or “fructose/glucose/galactose,” [ 13,18 ] which clearly limits interpretability. In addition to glucose, sugar compounds identified as changing during the time course of an OGTT or that display altered levels in type 2 diabetes patients are 1,5‐anhydroglucitol, mannose, maltose, and glucuronic acid.…”

“…We therefore applied our semitargeted sugar profiling method, previously used for urine analysis, [ 19 ] to assess whether novel sugar compounds can be identified in plasma of healthy, prediabetic, and diabetic subjects in a fasted state and after an OGTT.…”