RT Journal Article
SR Electronic
T1 Plasma N-glycome shows continuous deterioration as the diagnosis of insulin resistance approaches
JF BMJ Open Diabetes Research & Care
JO BMJ Open Diab Res Care
FD American Diabetes Association
SP e002263
DO 10.1136/bmjdrc-2021-002263
VO 9
IS 1
A1 Ana Cvetko
A1 Massimo Mangino
A1 Marko Tijardović
A1 Domagoj Kifer
A1 Mario Falchi
A1 Toma Keser
A1 Markus Perola
A1 Tim D Spector
A1 Gordan Lauc
A1 Cristina Menni
A1 Olga Gornik
YR 2021
UL http://drc.bmj.com/content/9/1/e002263.abstract
AB Introduction Prediction of type 2 diabetes mellitus (T2DM) and its preceding factors, such as insulin resistance (IR), is of great importance as it may allow delay or prevention of onset of the disease. Plasma protein N-glycome has emerged as a promising predictive biomarker. In a prospective longitudinal study, we included patients with a first diagnosis of impaired glucose metabolism (IR or T2DM) to investigate the N-glycosylation’s predictive value years before diabetes development.Research design and methods Plasma protein N-glycome was profiled by hydrophilic interaction ultra-performance liquid chromatography in 534 TwinsUK participants free from disease at baseline. This included 89 participants with incident diagnosis of IR or T2DM during the follow-up period (7.14±3.04 years) whose last sample prior to diagnosis was compared using general linear regression with 445 age-matched unrelated controls. Findings were replicated in an independent cohort. Changes in N-glycome have also been presented in connection with time to diagnosis.Results Eight groups of plasma N-glycans were different between incident IR or T2DM cases and controls (p<0.05) after adjusting for multiple testing using Benjamini-Hochberg correction. These differences were noticeable up to 10 years prior to diagnosis and are changing continuously as becoming more expressed toward the diagnosis. The prediction model was built using significant glycan traits, displaying a discriminative performance with an area under the receiver operating characteristic curve of 0.77.Conclusions In addition to previous studies, we showed the diagnostic potential of plasma N-glycome in the prediction of both IR and T2DM development years before the clinical manifestation and indicated the continuous deterioration of N-glycome toward the diagnosis.Data are available upon reasonable request. The datasets used and analysed during the current study are available from the corresponding author on reasonable request.