Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.
Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Leipzig, Germany.
Diabetes Obes Metab. 2018 Nov;20(11):2661-2669. doi: 10.1111/dom.13449. Epub 2018 Jul 30.
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.
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.
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.
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.
游离脂肪酸（FFA）介导诸如碳水化合物代谢下调等不良代谢效应，为肥胖与 2 型糖尿病（T2DM）的发展之间的因果关系提供了依据。在这里，我们研究了 FFA 的血浆浓度，单独以及与蛋白质糖化相结合，作为 T2DM 的潜在诊断和预后生物标志物。
从 48 名新诊断的男性 T2DM 患者、48 名长期控制（24 名男性和 24 名女性）T2DM 患者、20 名糖尿病前期男性 T2DM 患者和两个年龄匹配的对照组（48 名非糖尿病（ND）男性；24 名男性和 24 名女性 ND 参与者）中采集 EDTA-血浆，用于分析包括 FFA 在内的一系列临床参数。糖化位点在胰蛋白酶消化后使用串联质谱进行定量。
与对照组相比，新诊断（长期控制）T2DM 患者的 FFA 血浆浓度中位数高出近三倍，诊断敏感性（SN）为 92%（85%），特异性（SP）为 90%（88%）。当与触珠蛋白赖氨酸 141 的糖化水平结合时，新诊断（SN，94%；SP 96%）和长期控制（SN，85%；SP，94%）T2DM 患者的诊断准确性进一步提高（HbA1c：SN，88%；SP，96%）。一项评估预后价值的前瞻性试点研究显示，糖尿病前期患者的 FFA 水平最初较低，但在接下来的四年中，那些糖尿病前期状态恶化或发展为 T2DM 的患者的 FFA 水平升高。
新诊断和长期控制的 T2DM 患者的 FFA 水平升高，分别提供了 87%和 91%的高诊断准确性，当与触珠蛋白赖氨酸 141 的糖化程度结合时，准确性进一步提高。此外，在发展为 T2DM 的患者中，FFA 的平均倍数变化高于 HbA1c 或 FPG，表明对疾病进展的敏感性更高。
