A Peptidomic Analysis of the Potential Comorbidity Biomarkers for Type 2 Diabetes Mellitus and Alzheimer’s Disease

Objective: To investigate the potential comorbidity biomarkers for Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD). Methods: This is a randomized case-control study. There are three groups: 1) normal control group included 32 healthy elderly people in the hospital physical examination; 2) 30 patients with T2DM group; and 3) AD group has 28 cases. On-line reversed-phase liquid chromatography separation, tandem mass spectrometry analysis and iTRAQ quantification were used for identification of peptidomic analysis, then detection of three comorbidity biomarkers might be associated with T2DM and AD by ELISA. Results: The Peptidomic Analysis of the potential comorbidity biomarkers for T2DM and the AD group includes Osteopontin (OPN), Isoform 2 of Histone H2Btype 2-F and Histone H4. These potential comorbidity biomarkers for T2DM and the AD group are significantly increased than normal control group. OPN concentrations are 1.67 (0.13 - 2.63) mmol/L in the normal control group, 3.15 (1.51 - 5.35) mmol/L in the T2DM group, and 7.66 (3.55 - 15.38) mmol/L in the AD group. Histone H4 concentrations in three groups respectively are 0.21 ± 0.036 mmol/L (normal control), 0.21 ± 0.046 mmol/L (T2DM) and 0.21 ± 0.034 mmol/L(AD). Isoforms 2 of Histone H2Btype 2-F are 1.73 (0.12 - 2.60) mmol/L, 4.71 (1.26 - 6.84) mmol/L and 9.30 (0 - 20.8) mmol/Lin three groups respectively. Conclusion: The inflammatory mechanism may lead to an increase of histone content in the urine of AD and T2DM patients. Clinical test of these potential comorbidity biomarkers Histones and Osteopontin would be the diagnosis of comorbidity AD and T2DM.