Type 3 Diabetes – (Less) Food For Thought?

With pre-diabetes and diabetes both increasing at astronomically high rates, new research delineates the direct correlation between sugar imbalance and Alzheimer’s disease (AD). Physicians are taught that diabetes can have an adverse effect on the kidneys, cardiovascular and nervous system. One organ that gets less attention with regard to poor blood sugar control is the brain. Research confirms that increased body mass index and diabetes, which are a result of a diet higher in carbohydrates, have been associated with AD, the most common form of dementia.

A recent study elucidated this phenomenon. Fifty healthy subjects (mean age of 60) were placed into one of three groups: 30 % caloric restriction, 20% increase in omega-3 fatty acid intake, or no dietary change. An impressive conclusion to this small but important study was that the group that was calorically restricted had a significant improvement in verbal memory of 20% (1). In addition, after 3 months, it was found that weight, fasting insulin levels, and highly-sensitive C-reactive protein levels (a marker of inflammation around heart tissue) decreased only in the caloric restriction group, but not in the other two groups.

It should be brought to light that the FDA would probably have approved any pharmaceutical that promised a 20% improvement in verbal memory. Diet modification may be a safer way of attaining the same goal. Physicians and nutritionists should strongly consider incorporating the results of this study when advising AD patients on diet. A healthy diet is not just for the heart, but for the brain as well.

The above research has its roots in a groundbreaking study referred to as the Rotterdam study published in 1999 in the journal Neurology (2). The study showed that diabetes mellitus almost doubled the risk of having AD. The novel term “Type 3 diabetes” links insulin resistance with AD.

In type I diabetes, there is a paucity of insulin production, which requires patients to resort to insulin injections to help regulate glucose levels. In type II diabetes, there is a resistance on a cellular level to the insulin that is being produced. These patients require a strict low-glycemic index diet and medication as needed. Sometimes, with poorly controlled type II diabetes, insulin is required as well. Type-3 diabetes harbors elements of both type-1 and type-2 diabetes in that there is both a decrease in the production of insulin and a resistance to insulin receptors.

Type-3 diabetes was coined by Dr. Suzanne de la Monte, a neuropathologist at Brown medical School in 2005 (3). Dr. de la Monte and her team looked at post-mortem brain tissue of patients who suffered from AD and found that AD may actually be a neuroendocrine disease associated with insulin signaling.

In addition to regulating blood sugar levels, insulin functions as a growth factor of all cells, including neurons in the brain. Thus, insulin resistance or lack of insulin, contributes to degenerative processes in the brain (4).

A group of researchers at Northwestern University found the probable mechanism of action behind why brains of AD patients are both low in and resistant to insulin. According to Dr. William Klein, who led the research, a neurotoxic molecule called ADDL (amyloid beta-derived diffusible ligand) may be responsible for the phenomenon. ADDLs are what help to explain why Alzheimer’s patients have lowered insulin levels as well as insulin resistance in their brains.

In healthy brains, insulin binds to a receptor at a synapse, a specialized junction connecting cells that allows them to communicate with one another. Once this occurs, a mechanism is initiated that allows for memories to form. It was found by Dr. Klein’s team that ADDLs, however, disrupt this mechanism of communication (5). ADDLs bind at the synapses, changing their shape. Because their shapes are altered, insulin cannot efficaciously bind at the synapses like they normally would. This, in turn, makes the cells insulin resistant, like in type II diabetes.

Applying this constellation of new medical research proactively is critical, especially when the intervention is benign. Neglecting to recommend simple dietary changes to an AD patient can be potentially detrimental, leading to rapid cognitive decline. Diet and other lifestyle changes should not be overlooked when treating Alzheimer’s disease.


1. Witte AV et al. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 2009 Jan 27;106:1255.
2. A. Ott et al, Diabetes and the risk of Dementia: Rotterdam Study, Neurology 1999; 53: 1937
3. de la Monte, Journal of Alzheimer’s Disease, March 2005
4. Li L, Holscher C. Common pathological processes in Alzheimer disease and type 2 diabetes: a review. Brain Res Rev. 2007 Dec;56(2):384-402. Epub 2007 Sep 11
5. Alzheimer’s disease-affected brain: Presenc

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