oa Systems Approach Towards Diabetes Research Using Molecular profiling Tools

The prevalence of insulin resistance and diabetes has shown a dramatic worldwide increase. In Qatar, the prevalence of diabetes is twice that of the United States today, possibly due to lifestyle and dietary changes. Diabetes has an enormously adverse impact on the afflicted population leading to patient mortality, morbidity and staggering health care costs to the nation. Untreated or inadequately treated diabetes results in serious health complications including eye, heart, kidney and nerve damage.

Mass spectrometry based molecular profiling is a powerful tool for interrogation of the underlying molecular alterations which define the etiology and patho-physiology of a complex disease such as diabetes. As a part of the QNRF funded study, we have used ultra performance liquid chromatography (UPLC) in conjunction with high resolution quadrupole time of flight mass spectrometry (Q-TOFMS) for proteomic and metabolomic profiling of bio-fluids derived from diabetic and healthy individuals recruited at the Qatar University Hopsital. The overall goal of this project was to investigate the changes in the molecular profiles in the two groups (normal and diabetic) at the protein and small molecule metabolite level and correlate these changes to define putative biomarkers with potentially diagnostic or prognostic clinical value. We have used a “smart pooling strategy” for bio-fluids from each group to enhance disease associated differences. LCMS/MS based metabolomic analysis of the diabetic and normal pre and post meal metabolome was followed by bioinformatics analysis to identify dysregulated metabolites. Additionally, we have used iTRAQ based UPLC-QTOFMS/MS for quantitative proteomic profiling.

These data were taken together for integrated functional pathway analysis to correlate the changes. Furthermore, we have used a validation cohort for targeted quantitation of candidate markers using multiple-reaction monitoring mass spectrometry. The results will be discussed in context of the state of art technology used for studying pathway perturbations resulting in a diabetic phenotype. A part of this study reported at the HUPO2010, won a “young investigator award” for Dr. Cheema. The ARF presents a unique opportunity to present results from this exciting study, deliberate upon the challenges faced and elaborate on the plans for future studies aimed at a mechanistic insight.