Type 3 diabetes

Type 3 diabetes (i.e., T3D) has been suggested to be an alternate name for a certain form of Alzheimer's disease (i.e., AD) in individuals with type 2 diabetes (i.e., T2D).^[1] AD accounts for 60% to 80% of all dementias. It currently afflicts 55 million individuals and is expected to afflict 139 million by the year 2050.^[2] There are two forms of AD. Early-onset Alzheimer's disease (i.e., EOAD) generally afflicts individuals between 45 to 65 years of age and accounts for 5% to 6% of all AD cases. About 10-20 % of EOAD cases are due to inheriting a defective gene (see Early onset AD). The remaining cases of EOAD are associated with various risk factors such as head injuries, cardiovascular diseases, chronic schizophrenia, the Down syndrome, and lifestyle features such as poor diets, smoking, alcohol use, and sedentary lifestyles.^[2][3] The other form of AD is termed late onset AD (i.e., LOAD). It is typically diagnosed in individuals more than 64 years old. LOAD is caused by neuroinflammation in certain areas of the brain which result in the formation of excessive phosphorylation of proteins such as the Tau protein and the accumulation of plaques (i.e., misfolded and clumped protein fragments of the amyloid beta protein i.e., Aβ) in brain neurons. The formation of these and other proteins can cause the dysfunction of brain neurons.^[4] It is the form of AD associated with T2D: LOAD is almost twice as common in individuals who have T2D. A study done in the USA found that there were 71,550 deaths between 1999 and 2019 among individuals who had both LOAD and T2D. Because the brain tissues of individuals with LOAD are abnormally resistant to insulin's stimulation of neurons, some studies have termed LOAD in individuals with T2D as T3D. This is based on the idea that T2D causes LOAD.^[1][4][5][6] T2D is a disease in which the tissues of individuals are insulin resistant and their β-pancreatic cells are functionally impaired. It afflicts about 10% of the world's population. T2D that afflicts brain neurons is suggested to be the cause for T3D.^[1][2][7][5] The insulin resistance that develops in brain neurons deprives these neurons of the glucose needed for survival. This leads to progressively increasing neuronal death, memory impairment, cognitive decline, and, ultimately, the dementia diagnosed as LOAD.^[1] T2D includes 90% of all diabetes cases, occurs most often in adults who are obese and do not exercise, and requires insulin and/or dietary treatments.^[8] There are two other types of diabetes. Type 1 diabetes is due to the death of the insulin-producing beta cells in the pancreas caused by an autoimmune system's attack and killing of the insulin-producing pancreatic beta cells (i.e., β-cells). It most commonly develops in childhood and adolescence, accounts for 5-10% of all diabetes cases, and involves the production of autoantibodies that kill the insulin-producing beta cells in 90% to 95% of these patients. It is treated with insulin therapy.^[9] Type 3c diabetes (i.e., T3c, also termed pancreatogenic diabetes) involves 1-9% of all diabetic cases. It is caused by injuries to the pancreas due to, e.g., pancreatitis, pancreatic ductal adenocarcinoma (pancreatic ductal carcinoma is the most common form of pancreatic cancer), cystic fibrosis, brocalculous pancreatic disease, and surgical removal of the pancreas.^[10]

AD is distinguished from other forms of dementia. Vascular dementia (i.e., VD) is the second most common form of dementias. It is caused by the damaging of key blood vessel due to stroke, atherosclerosis, and various other cardiovascular diseases.^[11][12] Other forms of dementia are regarded as a subtype of "Alzheimer's disease-related dementias" (i.e., ADRDs). ADRDs consists of 4 other forms of dementia: VA, Lewy body dementia (which is subclassified as dementias with Lewy bodies), Parkinson's disease dementia, and frontotemporal dementia.^[13] Gestational diabetes (i.e., GD) is a form of diabetes that develops in females during but then resolves after their pregnancy. There is a 10-fold increased risk that GD-afflicted females will develop T2D compared to those without GD and the offspring of individuals with GD also have an elevated risk for developing T2D.^[14] GD is in generally not considered in studies of T2D and dementias. Since many studies on T2D did not clearly define LOAD and may have included some patients with EODM, the following sections will use the term DM for the studied patients.