PMID- 29943387 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20190415 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 20 IP - 11 DP - 2018 Nov TI - Plasma levels of free fatty acids correlate with type 2 diabetes mellitus. PG - 2661-2669 LID - 10.1111/dom.13449 [doi] AB - 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. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Spiller, Sandro AU - Spiller S AD - Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universitat Leipzig, Leipzig, Germany. AD - Center for Biotechnology and Biomedicine (BBZ), Universitat Leipzig, Leipzig, Germany. FAU - Bluher, Matthias AU - Bluher M AD - University Hospital Leipzig, Department of Internal Medicine, Endocrinology and Nephrology, Universitat Leipzig, Leipzig, Germany. FAU - Hoffmann, Ralf AU - Hoffmann R AUID- ORCID: 0000-0001-9932-5646 AD - Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universitat Leipzig, Leipzig, Germany. AD - Center for Biotechnology and Biomedicine (BBZ), Universitat Leipzig, Leipzig, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180730 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Fatty Acids, Nonesterified) RN - 0 (HP protein, human) RN - 0 (Haptoglobins) SB - IM MH - Adult MH - Biomarkers/*blood MH - Blood Glucose/metabolism MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/*blood/*diagnosis MH - Fatty Acids, Nonesterified/*blood MH - Female MH - Haptoglobins/metabolism MH - Humans MH - Male MH - Middle Aged MH - Pilot Projects MH - Prediabetic State/blood/diagnosis MH - Predictive Value of Tests MH - Sensitivity and Specificity OTO - NOTNLM OT - biomarker OT - free fatty acids (FFA) OT - glycation sites OT - non-esterified fatty acids (NEFA) OT - plasma proteins OT - protein glycation OT - type 2 diabetes mellitus EDAT- 2018/06/27 06:00 MHDA- 2019/04/16 06:00 CRDT- 2018/06/27 06:00 PHST- 2018/01/31 00:00 [received] PHST- 2018/06/21 00:00 [revised] PHST- 2018/06/22 00:00 [accepted] PHST- 2018/06/27 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/06/27 06:00 [entrez] AID - 10.1111/dom.13449 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Nov;20(11):2661-2669. doi: 10.1111/dom.13449. Epub 2018 Jul 30.