NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus.

Laura Del Coco,Emanuela Mensà,Sara Bravaccini,Daniele Vergara,Fabiola Olivieri,Andrea Casadei-Gardini,Andrea Ragusa,Francesca Pirini,Anna Maria Giudetti,Jacopo Sabbatinelli,Anna Rita Bonfigli,Michele Maffia,Massimiliano Bonafè,Francesco Paolo Fanizzi,Gianluca Storci,Francesco Prattichizzo,Serena De Matteis

doi:10.3390/jcm8050720

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.

Highlights

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia associated with impairments in carbohydrate, lipid, and protein metabolism [1]
Three different selected groups of subjects were included for this investigation: non-diabetic subjects, referred as the control group (CG) and two different groups of Type 2 diabetes mellitus (T2DM) patients, with or without complications and insulin treatment
Patients with complications on insulin monotherapy were indicated as T2DM disease in patients with complications (T2DM-C); patients without complications and treatments were indicated as T2DM-NC

Summary

Introduction

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia associated with impairments in carbohydrate, lipid, and protein metabolism [1]. Environmental and lifestyle changes in association with populations aging account for the rapid global increase in T2DM prevalence and incidence in recent decades [3]. Chronic hyperglycemia leads to many long-term complications, such as cardiovascular disease (CVD), cerebrovascular disease, peripheral vascular disease, neuropathy, retinopathy, and renal failure, resulting in increasing disability, reduced life expectancy, and increased health costs [5]. The prognosis of patients with T2DM is highly dependent on the development of complications; the prevalence of patients with cardiovascular complication is growing exponentially and most T2DM patients die as a result of cardiovascular causes

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