A Comprehensive Review of Intranasal Insulin and Its Effect on the Cognitive Function of Diabetics

Abstract

Diabetes mellitus continues to be a disease that affects a good percentage of our population. The majority affected need insulin on a day-to-day basis. Before the invention of the first manufactured insulin in 1978, dealing with diabetes took a significant toll on patient's lives. As technology and human innovation prevail, significant advancements have taken place in managing this chronic disease. Patients have an option to decide their mode of insulin delivery. Intranasal insulin, one such form, has a rapid mode of action while effectively controlling postprandial hyperglycemia. It has also been proven to reduce hypoglycemia and insulin resistance problems, which seem to be the main adverse effects of using conventional insulin regularly. However, due to the large dosages needed and high incurring costs, Intranasal Insulin is currently being used as adjunctive therapy along with conventional insulin.We conducted a literature search in PubMed indexed journals using the medical terms "Intranasal insulin," "diabetes," and "cognitive impairment" to provide an overview of the mechanism of action of Intranasal Insulin, its distinctive cognitive benefits, and how it can be compared to the standard parenteral insulin therapy. One unique feature of intranasal insulin is its ability to directly affect the central nervous system, bypassing the blood-brain barrier. Not only does this help in reducing the peripheral side effects of insulin, but it has also proven to play a role in improving the cognitive function of diabetics, especially those who have Alzheimer's or mild cognitive impairment, as decreased levels of insulin in the brain has been shown to impact cognitive function negatively. However, it does come with its limitations of poor absorption through the nasal mucosa due to mucociliary clearance and proteolytic enzymes, our body's natural defence mechanisms. This review focuses on the efficacy of intranasal insulin, its potential benefits, limitations, and role in cognitive improvement in people with diabetes with pre-existing cognitive impairment.

Efficacy of intranasal insulin in improving cognition in mild cognitive impairment or dementia: a systematic review and meta-analysis

“…This has been demonstrated to contribute to enhancing the cognitive performance of diabetics, particularly those who have Alzheimer's disease or MCI, as it has been demonstrated that decreasing insulin levels in the brain have a detrimental effect on cognitive function. This helps to reduce the peripheral side effects of insulin in addition to reducing them (Gaddam et al, 2021 ). Yet, significant open questions remain about the safety, efficacy, and potential of insulin as an adjunct or monotherapy (Chapman et al, 2018 ).…”

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

“…The first, most extensive group consists of experimental and clinical studies to study the restorative effect of INI on the functional activity of different brain regions, neuronal networks, and cognitive functions, and significant progress has been made in this regard. The second, relatively small group consists of works devoted to the ability of INI to improve hormonal and metabolic parameters in DM and restore the functions of peripheral organs and tissues [ 29 , 36 , 276 ].…”

“…To date, there is a large amount of experimental data, as well as clinical observations, indicating the effectiveness of INI in the treatment of AD, Parkinson’s disease, and mild cognitive impairment, as well as neuropathies [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. It has also been shown that INI can improve memory in healthy subjects [ 42 , 43 , 44 ], which can be used to restore their cognitive abilities in case of overwork, psycho-emotional exhaustion, sleep restriction, and other physiological conditions leading to transient, reversible cognitive decline, and mood deterioration.…”

Pharmacomodulation of brain neuromedin U signaling as a potential therapeutic strategy

“…Oxytocin may also be helpful for selected group of patients suffering from post-traumatic stress disorder (PTSD) (Szafoni & Piegza, 2022), postpartum depression (Lindley- Baron-Cohen et al, 2022), autism spectrum disorder (ASD) (Plemeniti et al, 2021), and memory impairments (Zhao et al, 2019). Transnasally applied insulin not merely decrease blood glucose level, but it can also improve memory in healthy individuals and those suffering from Alzheimer's disease (AD) (Gaddam et al, 2021). Exendin, a long-acting glucagon-like peptide-1 receptor agonist, leading to increased insulin release is approved for use in adults with type-2 diabetes as an adjunctive therapy for those taking metformin and/or a sulfonylurea (Zhai et al, 2020).…”