Type 3 Diabetes Mellitus: A Link Between Alzheimer's Disease and Type 2 Diabetes Mellitus

Abstract

Chronic diseases, as their name suggests, are progressive and can have overlapping features. Similar to this, Alzheimer's disease (AD) and diabetes mellitus (DM) fall into the category of chronic degenerative diseases. The global burden of these two ailments is manifold; hence, it seems important to view the pathophysiologic mechanisms of DM in the worsening of AD. Genetic as well as environmental factors are seen to play a role in the disease pathogenesis. Several genes, metabolic pathways, electrolytes, and dietary habits are seen to hasten brain atrophy. Lying behind this is the accumulation of amyloid precursor and tauthe misfolded proteins-within the brain substance. This mechanism is usually innate to AD itself, but the impact of insulin resistance, disturbing the homeostatic milieu, is seen as a powerful contributing factor aggravating the neuronal loss impairing an individual's memory. Since this neuronal loss is permanent, it may lead to complications as seen with AD. To reach a consensus, we conducted an electronic literature review search using different databases. This aided us in understanding the common aspects between AD and DM on genetic, molecular, cellular levels, as well as the impact of minerals and diet on the disease manifestation. We also found that despite exceptional work, additional efforts are needed to explore the relationship between the two entities. This will help physicians, researchers, and pharmaceuticals to frame remedies targeting the cause and avoid the progression of AD.

Effect of a Community Gerontology Program on the Control of Metabolic Syndrome in Mexican Older Adults

“…The detection, prevention, and treatment of MS are of great relevance in old age, due to its magnitude and the high risk for diabetes mellitus, cardiovascular diseases, neoplastic diseases, cognitive deterioration, and Alzheimer’s disease (AD). In relation to this, the concept of “diabetes mellitus type 3” or “diabetes of the brain” has been proposed, to highlight the relationship between the pathophysiological process of DM2 and AD linked to MS, considering that hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, and chronic inflammation caused by MS influence and enhanced by aging (inflamm-aging) occurs in both diseases [ 28 , 29 , 30 ].…”

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

“…Accordingly, patients with Cushing syndrome present with whole-body insulin resistance [23,24]. The relationship between insulin resistance and AD, also called T3DM [15,16], is well recognized [12][13][14] and a subject of ongoing research. In this perspective, a recent epidemiological study has reinforced the detrimental role of chronic stress in T3DM and neurodegeneration [53].…”

“…However, there is increasing epidemiological evidence of the association between metabolic and dementia syndromes [7][8][9][10][11]. More specifically, systemic insulin resistance is postulated to be an important factor in the pathophysiology of AD, a phenomenon also called type III diabetes mellitus (T3DM) [12][13][14][15][16][17]. Although insulin resistance was long considered a central feature of type II diabetes mellitus (T2DM), previous studies showed its contribution and presence in the AD brain in the absence of T2DM [17].…”

Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

“…Moreover, the persistent condition of insulin resistance may alter the neuronal homeostatic milieu, thus exacerbating brain atrophy ( 65 ). Indeed, the sustained dysfunction of insulin/IGF-1 signaling within the central nervous system negatively impacts cell functionality and viability, thus triggering a pathogenetic cascade, as observed in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) ( 66 ). Physiologically, both insulin and IGF-1 exert neurotrophic effects by promoting myelin sheath synthesis, astrocyte glycogen storage, oligodendrogenesis and neuronal survival ( 67 , 68 ), thus guaranteeing neuronal plasticity.…”