http://www.ucd.ie/conway/html/homep...ticle_jun02.htm

UCD Team Makes Breakthrough in Slowing the Spread of Diabetes

Science Today - The Irish Times, 6th June 2002

Research at University College Dublin may open up new treatments for type II diabetes, a disease on the increase across the world. Dick Ahlstrom reports.

Scientists at University College Dublin are trying to unlock the biochemical steps that lead to type II diabetes. The work could lead to novel ways of tackling this difficult disease.

The work is timely given the rapid growth in the number of people developing type II diabetes. There are about 100,000 cases in the Republic and 200 million worldwide. Yet these numbers are expected to double within the next 20 years as a result of environmental, lifestyle and dietary choices in the 21st century, says Dr Philip Newsholme, of UCD's Department of Biochemistry within the Conway Institute of Biomolecular and Biomedical Research.

Diabetes is a disease in which the body loses its ability to regulate levels of sugar in the bloodstream. The hormone, insulin, handles sugar control, but diabetics don't produce enough insulin to keep sugar levels balanced.

There are two main forms of the disease. Type I diabetes tends to emerge during childhood and requires daily insulin injections. With this form of the disease, the islet beta-cells that make insulin die off.

Type II arises much later in life and is usually controlled by strict regulation of the diet and tablets. The beta-cells in this form don't die off but lose the ability to produce enough insulin. "Nobody knows in type II diabetes what goes wrong with the beta-cells," says Newsholme. "They simply become dysfunctional."

He decided to look at the biochemistry of the beta-cell and three years ago joined in a study with Prof Peter Flatt, head of the University of Ulster's diabetes research group. They won a North-South research co-operation grant from the Health Research Board. "It has established a co-operative link between our two labs," says Newsholme.

"We wanted to understand how nutrients stimulate insulin production from the beta-cells. They normally respond to nutrients, particularly glucose by increasing insulin production."

The cells react to everything in the diet, however, not just glucose. The research team, which included Dr Lorraine Brennan, decided to follow up a finding from 10 years earlier suggesting that certain amino acids, nutrients in food, could increase insulin production.

"The effect of the amino acids have been largely unexplained so far," he says. The earlier study described a synergistic effect with insulin production boosted significantly by amino acids. "We wanted to see what this synergy was all about."

The team used beta-cell lines provided by Prof Flatt's group for a series of in vitro studies. Cells were exposed to sugar as glucose and the amino acid L-alanine for an hour and then killed. The products of cell metabolism were then analysed using nuclear magnetic resonance (NMR).

NMR is more familiar as an imaging technique in medical diagnostics. But the technology can also be used in biological research, for measuring concentrations of molecules in solution. UCD received a grant from the Wellcome Trust to buy the NMR biological analysis system, which is the only one of its kind on this island, says Newsholme.

The system uses carbon-13 as a reference substance. Concentrations of the various metabolites are calculated on the basis of C-13 content as the carbons transfer from one to the next. "You can follow the major products that have come as a result of metabolism," says Newsholme.

The synergistic effect of L-alanine was immediately apparent in the findings but still contained a surprise. The beta-cells secreted five times more insulin if the amino acid was present, but 20 times more if both L-alanine and glucose were present in vitro. The team published their findings on June 1st in one of the world's leading journals for research into this disease, Diabetes.

The research group hopes to bring its findings forward by using an in vitro, cell-based model of type II diabetes to study the enzymatic steps as the beta-cells respond to glucose. "In Type II you do have a failure in these pathways," says Newsholme.

Having a detailed understanding of these steps should unearth new drug targets for the control of the disease. Exposure to sustained, high glucose levels seems to switch the beta-cells off. If the trigger for this could be found, perhaps a drug could block this and turn the beta-cells back on.

The L-alanine work should help the team "identify which enzymatic steps are important for insulin secretion", explains Newsholme.

© The Irish Times

"Type II arises much later in life and is usually controlled by strict regulation of the diet and tablets. The beta-cells in this form don't die off but lose the ability to produce enough insulin. "Nobody knows in type II diabetes what goes wrong with the beta-cells," says Newsholme. "They simply become dysfunctional."

- its my understanding that Type 2 is not a problem with insulin production at all, but merely an advanced stage of insulin resistance where the pancreas produces more and more insulin to lesser effect. The solution as we all know is a simple case of adopting a low carb WOL which reduces the requirement for so much insulin in the first place and can over time improve insulin sensitivity. If I am right, doesn't that make most cases of type 2 much more of a symptom rather than a disease?

Cheers,

Malcolm

Can you say insulin resistance? Think about it, when your pancreas has to over-produce insulin, it starts to wear out and it becomes less and less efficient at producing insulin. This seems to be a no-brainer to me.

Actually, I think it's called type II diabetes while it's still insulin resistance and at that stage it's treated with pills. But when the pancreas wears out, the person with diabetes starts needing insulin shots, that's when it should really be called diabetes. Insulin resistance can be cured with low-carbing, when it graduates to insulin dependence, it may be too late -- I don't know.

I happen to know 2 people who needed insulin shots daily who are now low carbing and totally off all meds.

I suppose there is something there. Also I think Dr. Bernstein was a type 1 diabetic and I havent read the book but I think he managed to get off insulin from what I heard (though I could be totally wrong wrong on this one)

Yes! I am so glad to hear about the 2 people you know.

However, I don't think Dr. Bernstein can ever stop using insulin. Type 1 diabetics don't make their own insulin. But I remember reading that he has way outlived the predicted lifespan for Type 1 diabetics because of low-carbing.

Again, it is my understanding of type 1 - that some of the insulin producing cells in the pancreas are destroyed by what is thought to be an infection of some kind, but if it is diagnosed early enough it is possible to adopt a low carb diet which matches the reduced insulin output of the remaining healthy cells. If this action is not taken early enough those remaining healthy cells burn out trying and failing to keep up with the additional insulin production demands placed on a smaller number of cells.

The actual diagnosis of type 2 is based on the result of a fasting blood glucose test, and the actual definition of whether you area type 2 diabetic or 'merely' have prediabetes or have levels in the normal range are just a series of numbers;

Conventional Medicine’s Interpretation
Of Fasting Glucose Blood Tests

70-109 mg/dL . . . . . . . . .Normal glucose tolerance
110-125 mg/dL. . . . . . . . .Impaired fasting glucose (prediabetes)
126+ mg/dL . . . . . . . . .Probable diabetes

Given that you can change these numbers going low carb, it would appear you can also change your status as someone who has type 2 diabetes... or doesn't.

Which makes the American Diabetes Association's advice seem all the more insane;

"The message today: Eat more starches! It is healthiest for everyone to eat more whole grains, beans, and starchy vegetables such as peas, corn, potatoes and winter squash. Starches are good for you because they have very little fat, saturated fat, or cholesterol. They are packed with vitamins, minerals, and fiber. Yes, foods with carbohydrate -- starches, vegetables, fruits, and dairy products -- will raise your blood glucose more quickly than meats and fats, but they are the healthiest foods for you. Your doctor may need to adjust your medications when you eat more carbohydrates. You may need to increase your activity level or try spacing carbohydrates throughout the day."

Cheers,

Malcolm

It's just insane! What is possessing the ADA?

It's a convoluted mess: diabetics are more prone to heart disease, so they should stay away from fats, so they should eat more carbs...and gee, this is such a tricky disease!

It shows how one bad fallacy leads to several more.

This is all great information. I think the real message for us is that as long as we have pancreatic function, we can cure diabetes. I can remember hearing that diabetes was incurrable -- oh wait, they're still saying that aren't they!

As to Dr. Bernstein, I remember reading in the excerpts of his book on his website that by the time his diabetes was diagnosed, it was too late, his pancreas was gone. Also, he commented that the diet prescribed at the time just made it worse. And the reason he's alive today is that he "discovered" low-carbing.

Which makes the American Diabetes Association's advice seem all the more insane;

And not just the ADA

I took a look at the advice from other countries and it was the same "eat carbs"

Lez

You're right Lez.....it's the same everywhere, eat carbs, diabetic or not.

Amazing isn't it? They've been pushing carbs on diabetics over the past several years, and the incidence of diabetes related complications is on the rise. No one sees the connection?

25+ years ago when I was in school (nursing) we were taught that Type 2 was simply the pancreas wearing out. Some people were more susceptable to this, depending on family history, and others were felt to become diabetic earlier if they had high carb intake and poor diet.....but the general thought was that eventually, if we lived long enough, just about everyone would eventually become diabetic. If you didn't have a family history and/or ate well this might not happen until you were in your 80's or 90's or even older (and in those days not as many people lived to those ages) BUT, if you didn't have a healthy diet, ate a lot of sugars and starches you could "wear out" your pancrease even sooner.....add family history into the mix and you might even become diabetic before you hit 50!

Now, without high sugar and starch diets, look how young we're "wearing out" our pancreases!

Why does no one see the connection?

When you consider that by nature of their disease, diabetics are carbohydrate intolerant, I agree that it's insane advice to tell those people to eat more carbohydrates "because they're good for you" while freely admitting that it will spike your blood sugar and likely require you to need more medication. What are these people thinking?????
The assumption that fat, saturated fat and cholesterol are bad for you and getting vitamins, minerals and fiber will somehow mitigate the damage caused by constantly spiking blood sugars is negligent at best.
Which is better for a diabetic; getting adequate nutrition while maintaining normal blood glucose ranges (often without the aid of medications) or getting adequate nutrition while in the process sending your blood sugars all over the board and requiring an ever-increasing amount of medication to achieve even a modicum of control and going on to probably require additional medications due the the complications that will inevitably develop?
Good for the drug companines...bad for the diabetic.
Sorry for the rant, folks...this just happens to be huge peeve of mine.

How come the researchers want to find a drug to treat the pancreas when reducing the glucose, i.e. low-carbing, can prevent the damage in the first place?

The answer is right under their noses. Stop exposing your beta cells to high glucose levels.

<irony on>
Gee... you don't suppose if those beta-cells aren't swimming in sugar all day long they'd perform better?

When I read that sentence I thought the answer would simply be, don't expose the beta-cells to high gluscose levels. I guess that wouldn't make any money for drug companies though.