In-Depth Analysis Of Metabolic Phenotype By Studying Age- And Sex-Related Features Of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by chronic hyperglycaemia mainly explained by insulin resistance and impaired insulin. T2DM is a worldwide increasing disease – in 2013, the International Diabetes Federation estimated that 382 million adults suffered from T2DM and that by 2035 there will be 592 people affected. These worrisome numbers challenge biomedical research at identifying new biomarkers for the diagnosis. The purpose of this study was to analyse and integrate different sources of clinical data with glycomics data in controls, prediabetics and diabetics cohorts, in order to 1) identify the major sources of variation in both data sets, 2) visualize patterns in variables within- and between-omics, 3) determine whether the identified patterns cluster according to known biological sources or conditions, and 5) estimate an aging clock based on the clinical variables and N-glycans and apply it to assess whether the groups of prediabetic and diabetic patients show an accelerated aging as compared with control and between sexes. The analytical methods employed were two-way partial least squares and regression. Results indicate that 1) the phenomics and glycomics joint components are different among groups and sexes over age, 2) intra- and inter-correlations between joint PCs obtained point to a common N-glycan signature (instead of endophenotype-specific), and 3) T2DM patients are biologically older than prediabetics and controls, being this effect more evident for male patients. Our main conclusions are that i) a combination of N-glycans could be used as complementary tool for the early diagnosis of metabolic dysregulation and/or T2D, ii) glycan peaks (GP) 1, GP2, and GP6 are confirmed as markers of aging, while GP8 and GP10 appear associated with dyslipidemia, and iii) this is the first time that prediabetics and diabetics have been included in an aging clock, as pure “healthy” controls do not exist.