Type 2 Diabetes and Alzheimer's Disease: Investigation into the Genetic Linkages of Shared Pathologic Molecular Mechanisms
[Thesis]
Nnanabu, Thomas
Harvard University
2020
77 p.
ALM
Harvard University
2020
Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder which is characterized by elevated blood-glucose levels and it is increasing dramatically (Morris et al., 2012). More than 347 million people are affected by diabetes worldwide. The late recognition and insidious inception of this disease are the main cause of the large number of mortality and morbidity cases worldwide, especially in the developing countries like Pakistan (Azevedo et al., 2008). T2DM is linked with impairment of the cognitive function, and one of the adverse complications of T2DM is an enhanced possibility of developing Alzheimer's disease (AD) (Peila et al., 2002; Arranitakis et al., 2004). AD a neurodegenerative disorder is common among elderly people. The AD patient suffers from memory loss and decline in intellectual functions (Baglietto-Vargas et al., 2016). Recent studies have shown shared links between these two disorders. However, the crosstalk between these factors and the mechanisms underlying the diabetes-related CNS complication is still elusive. Thus, the study was designed, and T2DM, AD, and T2DM/AD patients and healthy subjects (controls) blood samples were collected from different collaborating hospitals of Islamabad, Rawalpindi, Lahore, and Abbottabad. A total number of 820 research participants: 250 controls, 450 T2DM, 100 AD, and 20 with both T2DM and AD were recruited and interviewed. Patient inclusion criteria: Patient Inclusion criteria include patients diagnosed with T2DM, AD and T2DM & AD both. Patient exclusion criteria: Patients who do not meet the above criteria were excluded from the study. Patients with type 1 diabetes, gestational diabetes and pregnant women were also excluded. All the samples collected were transported to Dr. Ghosh's Lab at the Department of Biology, Howard University, Washington DC with prior IRB approval by the Howard University Institutional Review Board (IRB-17-MED- 43) and ASAB (NUST) (Ref. Ni. 28/IRB dated April 20, 2016 as well as material transfers' agreements. The DNA samples were shipped through FedEx, and the RNA samples were shipped by a special logistics carrier (World Currier) with dry ice. The major goal of this study was to investigate shared genetic mechanisms associated with Type 2 Diabetes and Alzheimer's disease in Pakistani Population. This will open the way to several lines of investigation and will help to understand disease pathogenesis.