Melatonin or Glucagon-like Peptide 1 Administration (small benefit)
Frequency
Unknown
Type 3 diabetes is a proposed pathological linkage between Alzheimer's disease and certain features of type 1 and type 2 diabetes.[1] Specifically, the term refers to a set of common biochemical and metabolic features seen in the brain in Alzheimer's disease, and in other tissues in diabetes;[1][2] it may thus be considered a "brain-specific type of diabetes."[3] It was recognized at least as early as 2005 that some features of brain function in Alzheimer's disease mimic those that underlie diabetes.[4] However, the concept of type 3 diabetes is controversial, and as of 2021 it was not a widely or generally recognized diagnosis.[5]
Metabolic risk factors such as hyperglycaemia, oxidative stress and lipid peroxidation are common processes thought to be contributors to the development of Alzheimer's disease in people with diabetes.[6] But while insulin resistance is a risk factor for the development of Alzheimer's disease and some other dementias, causes of Alzheimer's disease are likely to be much more complex than being explained by insulin factors on their own, and indeed some patients with Alzheimer's disease have normal insulin metabolism.[7]
The techniques used to prevent the disease in patients with diabetes are similar to individuals who do not show signs and symptoms of the disease.[8] The four pillars of Alzheimer's disease prevention[9] are used as a guide for individuals of who are at risk of developing Alzheimer's disease. As with Alzheimer's disease more broadly, there is no cure for type 3 diabetes, but disease progression may be slowed with certain drugs.[5]
Alzheimer's disease is associated with a progressive decline in mental faculties. At early stages, forgetfulness, poor judgment, lack of awareness of date or location, and mood disturbances may be evident. This progresses to major difficulties in performing everyday tasks and recognizing familiar people. At later stages, the ability to speak is lost, and control of basic body functions is lost or greatly diminished.[10]
These symptoms may be exacerbated in individuals with pre-existing type 1 or type 2 diabetes. Individuals with type 1 diabetes are often diagnosed at a young age, usually between childhood and adolescence.[6] In some cases, brain development in these patients is negatively impacted, resulting in cognitive impairment earlier in life.[6] In type 2 diabetes, which is usually diagnosed later in life, patients often exhibit cognitive impairment that correlates with the length of time since initial type 2 diabetes onset, and with poor glycemic control.[6][11]
The observation that both types 1 and 2 diabetes can contribute to the development of Alzheimer's disease led to the hypothesis that Alzheimer's disease reflects a brain-specific "type 3" of diabetes.[11] This hypothesis is controversial and not widely accepted in the medical community;[5] neurologist and skeptic Steven Novella remarked that "it is silly to say that [Alzheimer's disease] should now be known as Type 3 diabetes—unless you are trying to reinforce a simplistic medical narrative by massively overemphasizing the role of diet in every disease."[12]
Insulin resistance is a reduction in the body's sensitivity to insulin, which is required for most cells to use glucose. Thus, in type 3 diabetes, the neurons lack sufficient glucose to function properly. This deficiency can lead to a decrease in memory, judgement and the ability to reason, which are key symptoms of Alzheimer's disease.[13]
Elevated cholesterol
Elevated serum cholesterol, specifically LDL cholesterol, is a risk factor for AD,[15] and a variant of the cholesterol transport protein apoE is the most common genetic risk factor for late-onset AD.[16] Treatment with statins, which inhibit cholesterol synthesis in the liver, has furthermore been shown to decrease risk for dementia of various types.[17] LDL cholesterol levels are also a known risk factor for type 2 diabetes,[18] and type 2 diabetes itself can lead to chemically-altered LDLs and an increased residence time of LDL cholesterol in the blood.[19]
Oxidative stress and lipid peroxidation
Hyperglycemia, which frequently occurs in diabetes, can lead to formation of advanced glycation end-products and reactive oxygen species (ROS) in the brain.[1] The resulting oxidative stress causes chemical changes in the protein and lipid molecules that are essential to brain function.[1] The brain, which contains a high proportion of polyunsaturated fatty acids and relatively low levels of antioxidant proteins like catalase and superoxide dismutase,[1] is especially sensitive to this oxidative stress. One of the main biomarkers of oxidative stress is lipid peroxidation, or the presence of reactive peroxide groups on fatty acid molecules. These peroxides disrupt the integrity of cell membranes, cause harmful chemical modifications of critical membrane proteins, and may lead to disorganization of microtubules,[20] contributing to dysfunction in brain cells.
Type 1 diabetes is typically detected at a young age and may have negative impacts on cognitive growth. In both forms of diabetes, microvascular complications and hyperglycaemia are mutual risk factors that are found to contribute to the cognitive decline in patients.[10]
Mediterranean diet, a diet based around fruit, vegetables, olive oil, nuts and seafood has been shown to lower the risks of Alzheimer's disease in patients.[9] Specifically, patients who followed this diet which is modeled on particular Mediterranean nations presented decreasing amounts of amyloid-beta plaques between their nerve cells in the brain,[23] signifying the cell connections within the brain were firing correctly. This diet also presented increases in the thickness in the memory division of the brain cortex in the formal and parietal lobes and areas of cognition such as language and memory.[23] Updated versions of the Mediterranean diet such as the DASH diet have been recommended for patients, adding juicing and supplements to the recommendation for patients.[23]
The administration of the hormone Glucagon-like Peptide 1 has shown to control the deregulation of glucosemetabolism in patients with Alzheimer's disease.[29] This hormone can recover cerebral dysfunction in diabetes induced Alzheimer's disease. The hormone Glucagon-like Peptide 1 can lessen the brain's inflamed reaction caused by amyloid beta oxidative stress.[14][29]Glucagon-like Peptide 1 can also increase the rate of neurogenesis within the brains of Alzheimer's patients.[14] Glucagon-like Peptide 1 has the possibility to increase the production of neurons to substitute impaired neurons within the brain.[14] This hormone can also decrease the brain's insulin resistance in Alzheimer's patients.[29]
^Steen, Eric; Terry, Benjamin M.; Rivera, Enrique J.; Cannon, Jennifer L.; Neely, Thomas R.; Tavares, Rose; Xu, X. Julia; Wands, Jack R.; de la Monte, Suzanne M. (2005). "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes?". Journal of Alzheimer's Disease. 7 (1): 63–80. doi:10.3233/JAD-2005-7107. PMID15750215. S2CID28173722.
^Förstl, H.; Kurz, A. (16 December 1999). "Clinical features of Alzheimer's disease". European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–290. doi:10.1007/s004060050101. PMID10653284. S2CID26142779.
^Montine, Thomas J.; Neely, M. Diana; Quinn, Joseph F.; Beal, M. Flint; Markesbery, William R.; Roberts II, L. Jackson; Morrow, Jason D. (1 Sep 2002). "Lipid peroxidation in aging brain and Alzheimer's disease". Free Radical Biology & Medicine. 33 (5): 620–626. doi:10.1016/S0891-5849(02)00807-9. PMID12208348.
.jpg)
