Glycated lysine-141 in haptoglobin improves the diagnostic accuracy for type 2 diabetes mellitus in combination with glycated hemoglobin HbA1c and fasting plasma glucose

Abstract

BackgroundRecent epidemiological studies indicate that only 30–50% of undiagnosed type 2 diabetes mellitus (T2DM) patients are identified using glycated hemoglobin (HbA1c) and elevated fasting plasma glucose (FPG) levels. Thus, novel biomarkers for early diagnosis and prognosis are urgently needed for providing early and personalized treatment.MethodsHere, we studied the glycation degrees of 27 glycation sites representing nine plasma proteins in 48 newly diagnosed male T2DM patients and 48 non-diabetic men matched for age (range 35–65 years). Samples were digested with trypsin and enriched for glycated peptides using boronic acid affinity chromatography. Quantification relied on mass spectrometry (multiple reaction monitoring) using isotope-labelled peptides as internal standard.ResultsThe combination of glycated lysine-141 of haptoglobin (HP K141) and HbA1c provided a sensitivity of 94%, a specificity of 98%, and an accuracy of 96% to identify T2DM. A set of 15 features considering three glycation sites in human serum albumin, HP K141, and 11 routine laboratory measures of T2DM, metabolic syndrome, obesity, inflammation, and insulin resistance provided a sensitivity of 98%, a specificity of 100%, and an accuracy of 99% for newly diagnosed T2DM patients.ConclusionsOur studies demonstrated the great potential of glycation sites in plasma proteins providing an additional diagnostic tool for T2DM and elucidating that the combination of these sites with HbA1c and FPG could improve the diagnosis of T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9145-1) contains supplementary material, which is available to authorized users.

Plasma levels of free fatty acids correlate with type 2 diabetes mellitus

“…Glycation sites previously identified in plasma proteins of patients with diabetes were quantified after tryptic digestion of plasma samples and consecutive enrichment by boronate affinity chromatography, using a recently optimized method with multiple reaction monitoring on an electrospray ionization mass spectrometer (ESI‐MS), coupled on‐line to reversed‐phase high‐performance liquid chromatography (RP‐HPLC) . The validated protocol quantifies 30 glycation sites in 9 plasma proteins with sensitivities in the low nanomolar range and high interday precisions, that is, coefficients of variation (CVs) below 20%.…”

“…cFFA levels were compared among four different age‐matched cohorts, that is, 20 individuals with prediabetes, 48 patients with newly diagnosed T2DM, 48 long‐term controlled T2DM patients and 48 non‐diabetic individuals. FFA levels were also evaluated in combination with other routine anthropometric and laboratory chemistry parameters and the glycation degrees of 30 plasma protein glycation sites recently reported to improve diagnostic accuracy in T2DM . Additionally, the ratios of total cholesterol to HDL‐c (total‐c/HDL‐c), TAG/HDL‐c, and LDL‐c/HDL‐c and TAG levels as known predictors of CVDs, diabetic kidney disease (DKD) and ischemic heart disease (IHD) were studied.…”

“…FFA levels were also evaluated in combination with other routine anthropometric and laboratory chemistry parameters and the glycation degrees of 30 plasma protein glycation sites recently reported to improve diagnostic accuracy in T2DM. 18,19 Additionally, the ratios of total cholesterol to HDL-c (total-c/HDL-c), TAG/HDL-c, and LDL-c/HDL-c and TAG levels as known predictors of CVDs, 20-23 diabetic kidney disease (DKD) 24 and ischemic heart disease (IHD) 25 were studied.…”

Protein Carbonylation and Glycation in Legume Nodules

“…Protein glycation is well characterized in mammals under several physiological conditions (Spiller et al, 2017). In humans (Homo sapiens), the formation of AGEs accompanies atherosclerosis and diabetes (Höhn et al, 2013).…”

Mining seed proteome: from protein dynamics to modification profiles

“…Indeed, it was shown that seed proteins undergo this kind of modification during prolonged storage (Strelec, Ugarcic-Hardi, and Hlevnjak, 2008) and accelerated ageing of seeds (Wettlaufer and Leopold, 1991). It is important to note that resulting advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs) are known to interact with immunoglobulin-like receptors for advanced glycation end-products (RAGEs), and to trigger inflammatory response in mammals.…”