Authors: Manjeet K Gill-Sharma PhD
Diabetes mellitus (DM) is a disease of the peripheral organs while Diabetes inspidus (DI) is a disease of the brain. Both forms of diabetes are characterized by excess levels of blood sugar or glucose. Whereas the former is due to insulin resistance or insufficiency the latter is due to insufficiency of hypophyseal anti-diuretic hormone (ADH). But the causes underlying the accumulation of glucose in circulation are different for DM and DI. Diabetes mellitus is of two types. While type1 diabetes (T1D) is due to autoimmune destruction of insulin-producing pancreatic islets of Langerhans (IL), type 2 diabetes (T2D) is a lifestyle disease due to exhaustion of IL to produce insulin in response to hyperglycemia. Whereas glucose fuel unavailability in the mitochondria leads to deficit of energy production in the form of ATP, its accumulation in blood leads to complications due to inflammatory damage to blood vessels. Recently, Alzheimer’s disease (AD) has been hypothesized to be type3 Diabetes (T3D), presumably caused by insulin resistance in the brain, an organ absolutely dependent upon glucose as fuel for ATP biosynthesis. Whereas AD and DM are characterized by dementia and cognitive decline respectively, their known cellular biomarkers are different namely neuronal amyloid peptide (APβ), Tau, glial TDP-43 for AD and islet amyloid polypeptide (IAPP) for DM. DM also has a genetic component namely HLA-DQB1, CTLA-4, INS genes. Biomarkers of insulin receptor (IR) desensitization/functionality like neuron-speccific GLUT-8 need to be demonstrated in mouse models of AD, DM and humans before irreversible senile dementia characteristic of AD can be equated with reversible cognitive decline of type 2 DM, for it may have additional yet unknown causes.
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