Diabetes and Alzheimer’s Disease – What’s The Link?




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Diabetes mellitus is an emerging global epidemic that affects millions of people worldwide. This systemic disease affects the blood sugar level causing far-reaching consequences for the human body.

Diabetes affects the blood vessels and nerves of the body and causes long-term complications. During the early stages of disease, the damage caused by the high blood sugar level is not very obvious but after several years of poorly controlled diabetes, every organ of the body starts to show the signs and symptoms of disease-related deterioration.

Diabetes can lead to dementia

Most of the complications of diabetes are well-known. They include coronary artery disease (damage to the heart), diabetic neuropathy (damage to the nerves resulting in pain or loss of sensation in the legs and hands, as well as formation of skin ulcers), diabetic retinopathy (damage to the eyes) and diabetic nephropathy (damage to the kidneys). Another serious complication of diabetes is stroke and this complication can present itself in the form of vascular dementia, a condition that occurs when the blood supply to the brain is affected. Vascular dementia is the second most common cause of dementia, the first being Alzheimer’s disease.

Studies have shown that people with diabetes are at an increased risk of developing vascular dementia. The reason seems straight forward: like any other blood vessel in the body, the cerebral blood vessels that nourish the brain are damaged by the excess of blood sugar. The damaged blood vessels fail to nourish the brain cells effectively thus leading to increased cell mortality and development of dementia symptoms. But what is the link between diabetes mellitus and Alzheimer’s disease?

Can diabetes mellitus lead to the development of Alzheimer’s disease?

Recent studies propose a common pathophysiology between diabetes and Alzheimer’s disease. The similarities in the pathophysiology have given way to the thought that Alzheimer’s disease could be viewed as a new form of diabetes mellitus. The reasons for such an implication are not so complex and are as follows.

  • Amyloid plaques are seen in diabetes and Alzheimer’s disease patients

The pathology of Alzheimer’s disease is still a hotly debated topic. However, researchers have proposed certain characteristic features of Alzheimer’s diseases that are attributed to the damage caused to the brain. They include the formations of certain protein deposits: amyloid plaques and neurofibrillary tangles. The interesting fact is that these deposits are also seen in the brain autopsies of patients who died with diabetes.

Localized amyloidosis is also a common pathological finding in the pancreas of diabetes patients and it has been attributed to the beta cell dysfunction. The beta cells of pancreatic islets secrete insulin and the alpha cells secrete glucagon. The primary function of these hormones is to maintain the blood sugar level. The beta cells also secrete a protein called islet amyloid polypeptide or amylin (IAPP). The action of amylin is to inhibit the secretion of insulin and glucagon. In type 2 diabetes these amyloid polypeptides get deposited in the pancreatic islets.

Furthermore, an association has been demonstrated between the extent of amyloid deposition and the reduction of beta-cell mass. A vicious cycle has been demonstrated: the insulin resistance seen in type 2 diabetes demands the pancreatic islets to secrete more insulin. This demand indirectly stimulates the beta cells to secrete more IAPP leading to amyloid deposition and beta cell dysfunction. The result is again a further reduction in insulin secretion.

  • Brain cells of Alzheimer’s patients exhibit marked insulin resistance

It is well known that insulin resistance is a characteristic feature of type 2 diabetes. The surprising fact is that insulin resistance is also evident in the brain tissues of Alzheimer’s disease patients.

Insulin is essential for the uptake of glucose by the cells of various tissues of the body and the brain tissues are no exception. Insulin receptors are abundant in the brain. Actually, they are found to be specifically expressed in the regions of brain that are concerned with cognitive functions.

Studies have identified a reduced expression of certain genes during the early stages of Alzheimer’s disease. They are none other but the genes that are responsible for the production of the hormones insulin and insulin-like growth factor and the genes that encode for the receptors of these hormones in the brain. These findings made the researchers suggest that Alzheimer’s disease is a form of diabetes mellitus that selectively affects the brain.

  • Oxidative stress and inflammation caused by diabetes mellitus can result in neuronal damage

The impaired insulin production and signalling mechanisms cannot be solely attributed to the pathogenesis of Alzheimer’s disease. The accompanying inflammatory responses that occur in diabetes are also proposed to contribute to the cascade of reactions that cause the brain damage.

Increased blood sugar level has also been proposed to increase oxidative stress that could lead to progressive damage to the brain. Neurons are highly dependent on ATP, a molecule that carries energy, for their effective function. Most of the ATP molecules are produced by the mitochondria. The increased oxidative stress found in diabetes patients affects mitochondrial function resulting in neuronal degeneration.

Anti-diabetic drugs in the treatment of Alzheimer’s disease

With several studies suggesting a possible association between diabetes mellitus and Alzheimer’s disease, various clinical trials are underway to establish an effective treatment strategy for Alzheimer’s disease.

There are controversial reports on the effects of insulin therapy on the cognitive functions of dementia patients. While some studies report that insulin therapy increases the risk of dementia in diabetes patients, other studies suggest that insulin therapy helps in slowing down the cognitive decline in Alzheimer’s disease patients. However, with regards to pathological findings, a combination therapy (insulin and oral hypoglycaemic medications) was found to have positive effects. This was evidenced by the decreased amount of the neuritic plaques in diabetes patients who received both insulin and anti-diabetic therapies.

With a possible intimate connection between the two disorders, and with a good number of studies suggesting a positive effect of anti-diabetic medications on cognitive functions, a common pharmacotherapy is expected to be effective in controlling the course and progression of these two disorders. However, researchers could not exclude the possibility that the beneficial effects of some anti-diabetic medications could be due to their intrinsic properties that are unrelated to their sugar-controlling effects.

Nevertheless, the markedly common pathophysiological features of the two disorders have generated much interest and the hope in that further research in this field would give way to the development of novel therapeutic strategies for the treatment of Alzheimer’s disease.

References

Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, & Raffa RB (2011). Diabetes mellitus and Alzheimer’s disease: shared pathology and treatment? British journal of clinical pharmacology, 71 (3), 365-76 PMID: 21284695

Beeri MS, Schmeidler J, Silverman JM, Gandy S, Wysocki M, Hannigan CM, Purohit DP, Lesser G, Grossman HT, & Haroutunian V (2008). Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology, 71 (10), 750-7 PMID: 18765651

De Felice FG (2013). Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. The Journal of clinical investigation, 123 (2), 531-9 PMID: 23485579

Huang CC, Chung CM, Leu HB, Lin LY, Chiu CC, Hsu CY, Chiang CH, Huang PH, Chen TJ, Lin SJ, Chen JW, & Chan WL (2014). Diabetes mellitus and the risk of Alzheimer’s disease: a nationwide population-based study. PloS one, 9 (1) PMID: 24489845

Hull RL, Westermark GT, Westermark P, & Kahn SE (2004). Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. The Journal of clinical endocrinology and metabolism, 89 (8), 3629-43 PMID: 15292279

Janson J, Soeller WC, Roche PC, Nelson RT, Torchia AJ, Kreutter DK, & Butler PC (1996). Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proceedings of the National Academy of Sciences of the United States of America, 93 (14), 7283-8 PMID: 8692984

de la Monte SM, & Wands JR (2008). Alzheimer’s disease is type 3 diabetes-evidence reviewed. Journal of diabetes science and technology, 2 (6), 1101-13 PMID: 19885299

Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, & Breteler MM (1999). Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology, 53 (9), 1937-42 PMID: 10599761

Peila, R., Rodriguez, B., & Launer, L. (2002). Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies: The Honolulu-Asia Aging Study Diabetes, 51 (4), 1256-1262 DOI: 10.2337/diabetes.51.4.1256

Plastino M, Fava A, Pirritano D, Cotronei P, Sacco N, Sperlì T, Spanò A, Gallo D, Mungari P, Consoli D, & Bosco D (2010). Effects of insulinic therapy on cognitive impairment in patients with Alzheimer disease and diabetes mellitus type-2. Journal of the neurological sciences, 288 (1-2), 112-6 PMID: 19836029

Westermark GT, & Westermark P (2013). Islet amyloid polypeptide and diabetes. Current protein & peptide science, 14 (4), 330-7 PMID: 23745697

Image via Lucky Business / Shutterstock.

  • http://www.themindbodyspiritstore.com Danny Zwolenski

    I hope this catches fire. I personally wonder why it takes so long for this to catch on. It sounds like “hey, there might be a link between diabetes and Alzheimer’s”. I watched my mom die from diabetes that led to severe dementia, I don’t believe there is any doubt that there is a connection.

    So I appreciate the information and hope it is not long before the link is validated by the mainstream so something can be done to help.

  • http://www.eastwoodcompanies.com Eastwood

    There is a definite connection between the two. Some researchers are recognizing Alzheimer’s disease as a complication of diabetes. They have discovered that insulin shields the brain from toxic proteins associated with Alzheimer’s disease. They theorize that Alzheimer’s may be a third form of diabetes.

    The brain is more vulnerable to toxins which cause Alzheimer’s with age. “As you get older, some individuals start to have less effective insulin signaling, including in the brain.” – WIlliams Klein

    To learn more about this topic, visit our website

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing.
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