Study links diabetes and Alzhelimer's

[Vince]

MADISON (WKOW) -- A new UW study has confirmed a link between Alzheimer's disease and diabetes.
Researchers with the UW School of Medicine and Public Health found people in the early stages of diabetes are showing signs of brain dysfunction by using brain scans of people with a family history of Alzheimer's disease. The research involved 150 members in the Wisconsin Registry for Alzheimer's Prevention (WRAP) over a two year period.
Dr. Barb Bendlin, the lead author, is an assistant professor of medicine at UW and a researcher for the Wisconsin Alzheimer's Disease Research Center. According to Bendlin, the findings showed high levels of insulin resistance in the brains of study participants and a reduced uptake of glucose.


Bendlin said the research confirms tests that had been done earlier on animals.

"In Alzheimer's disease, the brain shows low levels of insulin, which is important for memory function," Bendlin said. "One theory is that brain cells become insulin resistant, which is a feature of diabetes. The brain can't take up the sugar it needs, because it is not responding to insulin, or insulin levels in the brain may be low."



According to the American Diabetes Association, 27 percent of people aged 65 and older in the U.S. have diabetes and about half have pre-diabetes. People with diabetes face double the risk of developing Alzheimer's disease.


"The hypothesis is that diabetes is a risk factor for Alzheimer's disease, but not everyone with diabetes is going to get Alzheimer's," Bendlin said. "We're interested in how early interventions could protect people, and one of the things you could do to protect your brain is maintain proper blood sugar levels."



Bendlin's findings will be published in the journal Alzheimer's and Dementia, and during this week's Alzheimer's Association International Conference in Boston.http://www.wxow.com/story/22866575/...-link-between-alzheimers-disease-and-diabetes

 

[Vince]

http://www.westonaprice.org/modern-diseases/type-3-diabetes-metabolic-causes-of-alzheimers-disease/

DISCUSSION Like that of many of its complex neurodegenerative counterparts, AD research is stymied by the problem of identifying what the first steps are in a vicious cycle wherein an underlying disturbance is perpetuated by the very results of the disturbance. The physiological and biochemical changes observed in AD point to a brain that is struggling to maintain its viability. It downregulates the uptake of glucose, upregulates mechanisms to use alternative fuels, and increases production of protective substances.
Many researchers see the accumulation of Aβ as the triggering event in AD pathology. However, a more integrated view of the innate wisdom of the human body suggests that Aβ initially serves a protective role, just as a fever is a protective mechanism rather than something to be annihilated unquestioningly. Nevertheless, just as a fever spiking too high can create problems of its own, increasing numbers and density of Aβ plaques in a hyperglycemic brain can initiate chain reactions of glycation and oxidation that serve to exacerbate mitochondrial dysfunction, decreased ATP production, and cognitive decline.
It is unlikely that Aβ plaques are a primary causative factor in AD because the effects of reduced glucose uptake in the brain are observed long before the plaques are evident. The plaques more logically result from functional inhibition of IDE due to peripheral hyperinsulinemia. Some progressive researchers have suggested that insulin resistance at the BBB is the brain's way of forcing a slowdown in the metabolism of glucose. This seems illogical if glucose is the brain's primary fuel (assuming a carbohydrate-rich diet). Why would the brain seek to limit the uptake of its main fuel? Several mechanisms are at work, and they all indicate that the brain is protecting its own survival while trying to minimize further damage.
First, high levels of glucose in brain interstitial fluid are glycating. Glycated proteins and cellular structures have altered function, increased vulnerability to oxidative damage, and reduced degradation and clearance. Slowing the entry of glucose into the brain would delay these processes and possibly give the body's defenses more time to dispose of the AGEs.
Second, glucose metabolism causes a heavy burden of oxidative stress. The running of the mitochondrial electron transport system (ETS) is the greatest source of reactive oxygen species (ROS) and free radicals in the body, and neurons are particularly susceptible to oxidative stress because their metabolic rate is higher than that of other brain cells. Moreover, neuronal membranes are rich in long-chain PUFAs and cholesterol, which are highly vulnerable to oxidation. 22 AGEs have been shown to induce lipid peroxidation, so exposure of fragile membrane PUFAs to a hyperglycemic environment can be considered toxic. In an organ that is potentially so highly damaged from a lifetime of dietary and environmental abuse, downregulating the usage of a fuel whose metabolism creates even more damage can be seen as a last-ditch effort just to survive.
Third, the brain could be redirecting its metabolic machinery toward utilization of fuels other than glucose, such as fatty acids and ketone bodies, which produce less oxidative stress and are, in fact, more efficient fuels.
One way in which Aβ serves a potentially helpful role is that it upregulates production of amyloid-β-peptide-binding alcohol dehydrogenase, an enzyme capable of metabolizing alternative fuels such as ketone bodies and alcohols. Another possibly protective role for Aβ is in catalyzing the production of lactate dehydrogenase, which converts pyruvate to lactate under anaerobic conditions.Lactate is produced in glial cells and sent to neurons, where it is converted back to pyruvate and sent through the tricarboxylic acid (TCA) cycle to produce ATP. Up-regulating lactate production compartmentalized within the brain could be the struggling brain's way of providing a fuel substrate when glucose usage in the brain has been compromised. Here again we have two scenarios in which Aβ seems to be priming the brain to move away from glucose.