Aims: Free fatty acids (FFA) mediate adverse metabolic effects such as downregulated carbohydrate metabolisms, providing causal links between obesity and the development of type 2 diabetes mellitus (T2DM). Here, we investigated the plasma concentrations of FFA alone and in combination with protein glycation as potential diagnostic and prognostic biomarkers of T2DM.
Materials and methods: EDTA-plasma obtained from 48 newly diagnosed male T2DM patients, 48 long-term controlled (24 male and 24 female) T2DM patients, 20 prediabetic male T2DM patients and two age-matched control cohorts (48 non-diabetic (ND) men; 24 male and 24 female ND partipants) were analysed for a set of clinical parameters including FFA. Glycation sites were quantified after tryptic digestion using tandem mass spectrometry.
Results: Median plasma concentrations of FFA were almost three-fold higher in samples obtained from newly diagnosed (long-term controlled) T2DM patients than in those obtained from the control group, providing diagnostic sensitivity (SN) of 92% (85%) and specificity (SP) of 90% (88%). When combined with the glycation level of lysine-141 of haptoglobin, diagnostic accuracy improved further for newly diagnosed (SN, 94%; SP 96%) and long-term controlled (SN, 85%; SP, 94%) T2DM patients (HbA1c: SN, 88%; SP, 96%). A prospective pilot study evaluating the prognostic value revealed initially low FFA levels for pre-diabetic patients that increased in the following four years in patients whose prediabetic state worsened or who developed T2DM.
Conclusions: FFA levels are elevated in newly diagnosed and long-term controlled T2DM patients, providing high diagnostic accuracy of 87% and 91%, respectively, which improved further when combined with the glycation degree of lysine-141 in haptoglobin. Additionally, FFA showed higher mean fold-changes than HbA1c or FPG in subjects developing T2DM, indicating higher sensitivity towards the progression of the disease.
Keywords: biomarker; free fatty acids (FFA); glycation sites; non-esterified fatty acids (NEFA); plasma proteins; protein glycation; type 2 diabetes mellitus.
© 2018 John Wiley & Sons Ltd.