Metformine - diabetes drug for epilepsy acts like ketogenic diet?

[Bernard]

I thought this was interesting (and confirms my observation about the 3 seizure control diets - they all limit simple sugars):

... Now, in the new work, the researchers have identified a small molecule in the neurons that senses how much energy in available. Glucose turns on this sensor -- but so does Metformine, a FDA-approved prescription drug used by millions of people with diabetes to control their blood sugar. Dr. Roopra and his colleagues are now testing Metformine in the brains of mice to see how it affects the functioning of the hippocampus, the part of the brain involved with learning and memory and also the seat of seizures for many patients with epilepsy. The goal is to tamp down a mechanism called Long Term Potenciation enough to reduce the rate of epilepsy but not enough to affect the brain's ability to learn and remember.

At this early stage of the research, it appears to be hitting the right balance, says Dr. Roopra. In the meantime, he points out, there have been no reports of learning and memory side effects in any of the adults or children who have used Metformine for years.

The next step will be to take Metformine to a mouse model of epilepsy. It's still early, says Dr. Roopra, but the researchers already are pleased with the increased understanding of the likely mechanism of the positive effect of the ketogenic diet on epileptic seizures and the focus on new drug targets for this often-devastating disease. ...

Diabetes Drug May Hold Potential As Treatment For Epilepsy, Using Same Mechanism As Ketogenic Diet

 

[Dutch mom]

Experimental Agent Shows Promise as Safe, Effective Antiepileptic

By Caroline Cassels
Medscape Medical News 2006.
© 2006 Medscape
December 7 2006 (San Diego)

An experimental agent is showing promise as an effective and safe replacement for the ketogenic diet and may pave the way for a new class of drugs to treat temporal lobe epilepsy (temporal lobe epilepsy), a new study suggests.

Presented here at the First North American Regional Epilepsy Congress and published in the November 2006 issue of Nature Neuroscience (Garriga-Canut M et al. Nat Neurosci. 2006;9:1382-1387), researchers at the University of Wisconsin, in Madison, found the glycolytic inhibitor 2-deoxy-D-glucose (2DG) has anticonvulsant and antiepileptic properties in rodent models of epilepsy.

Although still in the experimental stages, the study's principal investigator, Avtar Roopra, PhD, told Medscape the study's findings are "very exciting" and may represent a breakthrough in temporal lobe epilepsy, which is commonly drug resistant.

The findings emerged unexpectedly when Dr. Roopra and colleagues were investigating the regulation of genes in the nervous system. Interested in exploring the relationship between neuronal excitability, gene-expression patterns, and metabolism, the investigators used 2DG simply as means of altering metabolism to reduce the rate of glycolysis in cells and ultimately determine the effect of altered metabolism on gene expression.

Dramatic Seizure Reduction

At the same time, he said, his colleague Tom Sutula, MD, an epileptologist, was trying to determine how metabolism in general and the ketogenic diet in particular affects the nervous system in epilepsy. For almost a century it has been known that the ketogenic diet, which eliminates carbohydrates, can be effective in treating epilepsy. However, the mechanisms by which it works are still unclear.

"We realized we were both looking at the same question from different angles, and that's when we got together and began to consider whether 2DG, which is the main glycolytic inhibitor, might not only control genes but may also be of therapeutic importance in epilepsy," said Dr. Roopra.

To explore this hypothesis, the researchers subjected rats to a kindling model of epilepsy. Repeated application of electrical stimuli generates brief electrographic seizures or afterdischarges, explained Dr. Roopra. Over time, focal behavioral seizures gradually evolve into generalized tonic-clonic seizures, causing permanent alterations in the neuronal circuitry.

When the investigators added 250-mg/kg 2DG to the rats' daily diet for 2 weeks before and during kindling, they observed a dramatic increase in the number of stimuli required to induce a given severity of seizure.

No Toxicity

"The whole [epileptogenic] process seemed to reverse itself. The amount of electric current required to induce a seizure actually went up and stayed up, and that was very, very exciting," said Dr. Roopra.

The mechanism behind the antiepileptic effect of 2DG lies in its ability to reduce glycolysis in the brain. This in turn reduces the expression of genes involved in epilepsy — specifically, brain-derived neurotrophic factor and track-B receptor.

"Basically we found we could control metabolism, and in doing so we could control genes involved in epilepsy, which resulted in epilepsy itself being controlled," he said.

Perhaps even more exciting, added Dr. Roopra, was that at 6-month follow-up there was no toxicity and no weight loss or effect on cognitive performance in the 2DG animals compared with controls. "This appears to be a very safe agent with no toxicity," he said.

Palatable Alternative

Up to 50% of epilepsy patients are refractory to drug treatment, and, of these, 50% respond to the ketogenic diet. However, this mode of treatment has several drawbacks.

Adherence to the high-fat, high-protein ketogenic diet — particularly in children, where it is often used — is a major challenge. Furthermore, deviation from the ketogenic diet can result in very severe seizures. 2DG, which has the added benefit of being sweet tasting, may offer patients a much more palatable alternative if it can be administered orally.

In addition, said Dr. Roopra there are major concerns regarding the long-term impact on overall health of consuming a high-fat, high-protein diet. However, if the animal-study results bear out, he said, the simple addition of 2DG to patients' daily regimen may make it possible for them to consume a normal, healthy diet.

Dr. Roopra said if all goes well, clinical testing of 2DG could begin as early as next year.


First North American Regional Epilepsy Congress: 60th Annual Meeting of the American Epilepsy Society
Abstract 4.098.
Presented December 4, 2006.

 

[alivenwell]

I just learned about another method that doctors accidentally discovered to help control glucose levels.

If the first section of the small intestine (right next to the stomach) is removed, diabetic patients can have a normal level of sugar. This sounds like a potential option to people who suffer from both diabetes and epilepsy.

The only concern I would have is whether the epilepsy medication is absorbed normally if part of the digestive system is removed.

 

[RobinN]

So what's the deal with insulin levels? Well, you need insulin to live, but you probably have far too much insulin floating around in your body. Most adults have about one gallon of blood in their bodies and are quite surprised to learn that in that gallon, there is only one teaspoon of sugar! You only need one teaspoon of sugar at all times -- if that. If your blood sugar level were to rise to one tablespoon of sugar you would quickly go into a hyperglycemic coma and die.

You body works very hard to prevent this by producing insulin to keep your blood sugar at the appropriate level. This reaction keeps you from dying when you eat sugar. Unfortunately, it turns out that high levels of insulin are quite toxic for your body. Anytime you eat grains and sugars, you are increasing your insulin levels. If you have high cholesterol, high blood pressure, diabetes, or are overweight, it is highly likely that you are eating far too many grains. When I reference diabetes I am referring to the most common type, type 2 diabetes, which typically occurs in adulthood and is associated with increased weight. Type 1 diabetes is actually a problem with not enough insulin, as the pancreas loses the ability to manufacture it.

http://www.mercola.com/nutritionplan/index2.htm#factor1

 

[Rohan15]

i think i know it.

I don't think IF would affect muscle mass much at all. If you go without food for a long period of time, say, several days, your metabolic system goes after your muscle mass to convert the protein stored there into the glucose you need to keep your blood glucose normal. This doesn't happen in the short term. All the protein structures in the body draw from and add to the amino acid pool. When muscle breaks down the individual amino acids go into the pool from where they're harvested by the system that converts them to glucose.
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Rohan

 

[RobinN]

Thanks for that clarity Rohan.