Abstract
In diabetes mellitus (DM), disorders of glucose and lipid metabolism are significant causes of the onset and progression of diabetic nephropathy (DN). However, the exact roles of specific lipid molecules in the pathogenesis of DN remain unclear. This study recruited 577 participants, including healthy controls (HCs), type-2 DM (2-DM) patients, and DN patients, from the clinic. Serum samples were collected under fasting conditions. Liquid chromatography-mass spectrometry-based lipidomics methods were used to explore the lipid changes in the serum and identify potential lipid biomarkers for the diagnosis of DN. Lipidomics revealed that the combination of lysophosphatidylethanolamine (LPE) (16:0) and triacylglycerol (TAG) 54:2-FA18:1 was a biomarker panel for predicting DN. The receiver operating characteristic analysis showed that the panel had a sensitivity of 89.1% and 73.4% with a specificity of 88.1% and 76.7% for discriminating patients with DN from HCs and 2-DM patients. Then, we divided the DN patients in the validation cohort into microalbuminuria (diabetic nephropathy at an early stage, DNE) and macroalbuminuria (diabetic nephropathy at an advanced stage, DNA) groups and found that LPE(16:0), phosphatidylethanolamine (PE) (16:0/20:2), and TAG54:2-FA18:1 were tightly associated with the stages of DN. The sensitivity of the biomarker panel to distinguish between patients with DNE and 2-DM, DNA, and DNE patients was 65.6% and 85.9%, and the specificity was 76.7% and 75.0%, respectively. Our experiment showed that the combination of LPE(16:0), PE(16:0/20:2), and TAG54:2-FA18:1 exhibits excellent performance in the diagnosis of DN.
Highlights
As a significant microvascular complication of diabetes mellitus (DM), both type 1 and type 2, diabetic nephropathy (DN) has become the leading cause of chronic kidney disease (CKD) [1, 2]
Without overfitting of the model (Supplementary Figure S2), the apparent separation among the healthy controls (HCs), 2 DM (2-DM), and DN groups, cumulative R2Y at 0.641 and Q2 at 0.359, indicated that the lipid metabolism pattern was changed among the three groups
DN is a diabetic complication characterized by progressive kidney damage
Summary
As a significant microvascular complication of diabetes mellitus (DM), both type 1 and type 2, diabetic nephropathy (DN) has become the leading cause of chronic kidney disease (CKD) [1, 2]. It has been reported that microalbuminuria progresses to macroalbuminuria in 50% of diagnosed DN patients without effective intervention and eventually develops into end-stage renal disease (ESRD) [7, 8]. According to the national health and nutrition examination survey (NHANES), the number of DN patients with an eGFR of < 60 ml/min/1.73 m2 but without albuminuria has increased over the past 30 years [10]. These patients’ annual mortality rate increased from 3.5% to 5.1% during this period [11]. It is urgently necessary to develop more accurate diagnostic markers for DN in the clinical setting
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