Abstract
ObjectiveTo monitor of type 2 diabetes more simply, conveniently and noninvasively, we are trying to identify the potential urinary peptides that associated with different stages of glucose control in type 2 diabetes mellitus.MethodsFirstly, we collected urine samples from type 2 diabetic patients and normal controls. These type 2 diabetic patients were divided into two groups according to fasting plasma glucose (FPG) and hemoglobin A1c% (HbA1c), respectively. Magnetic beads based weak cation exchange chromatography (MB-WCX) was used to condense urinary peptides. The eluates were then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Subsequently, ClinProt was used to profile and screen the polypeptide patterns based on different methods of grouping in diabetic patients and normal controls. Finally, the amino acid sequences of differentially expressed peptides were identified by nano-liquid chromatography-tandem mass spectrometry and the protein sources of the corresponding peptide were matched in IPI Human database.ResultsProteomics analysis found two up-regulated peptide (m/z 2756.1 and m/z 3223.2) representations in diabetic subjects, and the two peptides increased with increases in the amount of glycosylated hemoglobin. Further, the parallelism between m/z 3223.2 and glycosylated hemoglobin was better than the parallelism between m/z 2756.1 and glycosylated hemoglobin. Area under the receiver operating characteristic of the two peptides was 0.722 and 0.661, respectively. The above-mentioned peptide m/z 2756.1 was further identified as fragment of fibrinogen alpha chain precursor and m/z 3223.2 was fragment of prothrombin precursor.ConclusionThese results suggested the two urinary biomarkers enable monitor of type 2 diabetes patients with different stages of glucose control.
Highlights
Diabetes mellitus is a systemic metabolic disease characterized by hyperglycemia with insulin resistance and beta cell dysfunction
The amino acid sequences of differentially expressed peptides were identified by nano-liquid chromatography-tandem mass spectrometry and the protein sources of the corresponding peptide were matched in IPI Human database
Urinary Peptides in Type 2 Diabetes Mellitus. These results suggested the two urinary biomarkers enable monitor of type 2 diabetes patients with different stages of glucose control
Summary
Diabetes mellitus is a systemic metabolic disease characterized by hyperglycemia with insulin resistance and beta cell dysfunction. It was estimated that as many as 30% and up to 90% (data is diverse from country to country) of type 2 diabetes patients remained undiagnosed and often the onset of diabetes occurred 4–7 years or more before diagnosis [2, 3]. The clinical diagnosis and glucose intolerance evaluation rely on the measurement of glucose level: random fasting plasma glucose test (FPG), oral glucose tolerance test and hemoglobin A1c (HbA1c). Random fasting plasma glucose test requires an overnight fast, has high variability and lacks sensitivity. Oral glucose tolerance test is inconvenient and has weak reproducibility. Hemoglobin is the reflection of the glucose metabolism in the past six to eight weeks and cannot be used to diagnose diabetes. Measurement of hemoglobin A1c needs lysed erythrocytes and adds extra work for laboratory staff
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