Tom Blackwell, National Post

Published: Friday, December 15, 2006

In a discovery that has stunned even those behind it, scientists at a Toronto hospital say they have proof the body’s nervous system helps trigger diabetes, opening the door to a potential near-cure of the disease that affects millions of Canadians.

Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas.

“I couldn’t believe it,” said Dr. Michael Salter, a pain expert at the Hospital for Sick Children and one of the scientists. “Mice with diabetes suddenly didn’t have diabetes any more.”

The researchers caution they have yet to confirm their findings in people, but say they expect results from human studies within a year or so. Any treatment that may emerge to help at least some patients would likely be years away from hitting the market.

But the excitement of the team from Sick Kids, whose work is being published today in the journal Cell, is almost palpable.

“I’ve never seen anything like it,” said Dr. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies. “In my career, this is unique.”

Their conclusions upset conventional wisdom that Type 1 diabetes, the most serious form of the illness that typically first appears in childhood, was solely caused by auto-immune responses — the body’s immune system turning on itself.

They also conclude that there are far more similarities than previously thought between Type 1 and Type 2 diabetes, and that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn’s disease.

The “paradigm-changing” study opens “a novel, exciting door to address one of the diseases with large societal impact,” said Dr. Christian Stohler, a leading U.S. pain specialist and dean of dentistry at the University of Maryland, who has reviewed the work.

“The treatment and diagnosis of neuropathic diseases is poised to take a dramatic leap forward because of the impressive research.”

About two million Canadians suffer from diabetes, 10% of them with Type 1, contributing to 41,000 deaths a year.

Insulin replacement therapy is the only treatment of Type 1, and cannot prevent many of the side effects, from heart attacks to kidney failure.

In Type 1 diabetes, the pancreas does not produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the insulin that is produced is not used effectively — something called insulin resistance — also resulting in poor absorption of glucose.

The problems stem partly from inflammation — and eventual death — of insulin-producing islet cells in the pancreas.

Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an “enormous” number of nerves, pain neurons primarily used to signal the brain that tissue has been damaged.

Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick — injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.

“Then we had the biggest shock of our lives,” Dr. Dosch said. Almost immediately, the islets began producing insulin normally “It was a shock ? really out of left field, because nothing in the literature was saying anything about this.”

It turns out the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. Further study by the team, which also involved the University of Calgary and the Jackson Laboratory in Maine, found that the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a “vicious cycle” of stress on the islets.

So next they injected the neuropeptide “substance P” in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.

The islet inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one injection.

They also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar.

While pain scientists have been receptive to the research, immunologists have voiced skepticism at the idea of the nervous system playing such a major role in the disease. Editors of Cell put the Toronto researchers through vigorous review to prove the validity of their conclusions, though an editorial in the publication gives a positive review of the work.

“It will no doubt cause a great deal of consternation,” said Dr. Salter about his paper.

The researchers are now setting out to confirm that the connection between sensory nerves and diabetes holds true in humans. If it does, they will see if their treatments have the same effects on people as they did on mice.

Nothing is for sure, but “there is a great deal of promise,” Dr. Salter said.

How you prepare depends on where you’re going and for how long. Two weeks backpacking through Europe takes different planning than a week at the beach. Will you be crossing time zones? What kind of food will you eat and when? Will you be more active or less active than usual?

Getting Ready

Before a long trip, have a medical exam to make sure your diabetes is in good control. Schedule the exam with enough time to work on your control before you depart. Get immunization shots — if you need them — at least one month before you leave. If the shots make you sick, you’ll have time to recover before your trip.

Before any trip, get two papers from your doctor: a letter and a prescription. The letter should explain what you need to do for your diabetes, such as take diabetes pills or insulin shots. It should list insulin, syringes, and any other medications or devices you use. The letter should also list any allergies you have or any foods or medications to which you are sensitive.

The prescription should be for insulin or diabetes pills. You should have more than enough insulin and syringes or pills to last through the trip. But the prescription may help in case of emergency. In the United States, prescription rules may vary from state to state.

No matter where you go, wear a medical ID bracelet or necklace that shows you have diabetes. If you’re leaving the country, also learn how to say “I have diabetes” and “sugar or orange juice, please” in the language or languages of the countries you’ll visit.

Packing Tips

The second rule of travel for a person with diabetes: pack at least twice as much medication and blood-testing supplies as you think you need. Pack at least half in your carry-on bag so that your medication is always with you.

Whether you travel by car, plane, boat, bike, or foot, you’ll want to keep this “carry-on” bag with you at all times. Pack this bag with:

• all the insulin and syringes you will need for the trip
• blood and urine testing supplies (include extra batteries for your glucose meter)
• all oral medications (an extra supply is a good idea)
• other medications or medical supplies, such as glucagon, antidiarrhea medication, antibiotic ointment, antinausea drugs
• your ID and diabetes identity card
• a well-wrapped, air-tight snack pack of crackers or cheese, peanut butter, fruit, a juice box, and some form of sugar (hard candy or glucose tablets) to treat low blood glucose

Eating in the Air

When you fly, you can request a special meal low in sugar, fat, or cholesterol. Make your request at least two days before the flight. If you take insulin, wait until you see your food coming down the aisle before you take your shot. Otherwise, a delay in the meal could lead to low blood glucose. To be safe, always carry some food with you. If your meal is delayed or an order is mixed up, you won’t be stuck with an empty stomach.

Have Insulin, Will Travel

When you travel with insulin, give some thought to where you’ll be storing your supplies. Insulin does not need to be refrigerated. But insulin stored in very hot or very cold temperatures may lose strength. Don’t store your insulin in the glove compartment or trunk of your car. Backpacks and cycle bags can get quite hot in the direct sunlight. If you plan to travel by car or bike or to be out in the elements, take steps to protect your insulin. Many travel packs are available to keep your insulin cool.

In general, you should stick with the exact brand and formulation of insulin that you have been prescribed by your doctor. However, if you run out while you are on the road, and your regular brand is unavailable, you may substitute another brand’s equivalent formulation (for example, NovoLog for Humalog, Humulin R for Novolin R). Changes in formulation (for example, from rapid-acting Humalog to to short-acting Humulin R) require medical supervision.

Insulins used in the United States are all of the strength U-100. In foreign countries, insulins may come as U-40 or U-80. If you need to use these insulins, you must buy new syringes to match the new insulin to avoid a mistake in your insulin dose. If you use U-100 syringes for U-40 or U-80 insulin, you will take much less insulin than your correct dose. If you use U-100 insulin in a U-40 or U-80 syringe, you will take too much insulin.

Crossing Time Zones

If you take insulin shots and will be crossing time zones, talk to your doctor or diabetes educator before your trip. Bring your flight schedule and information on time zone changes. Your doctor or educator can help you plan the timing of your injections while you travel.

Remember: eastward travel means a shorter day. If you inject insulin, less may be needed. Westward travel means a longer day, so more insulin may be needed.

To keep track of shots and meals through changing time zones, keep your watch on your home time zone until the morning after you arrive.

If you inject insulin while in flight, frequent travelers suggest you be careful not to inject air into the insulin bottle. In the pressurized cabin, pressure differences can cause the plunger to “fight you.” This can make it hard to measure insulin accurately.

Checking your blood glucose while traveling is as important as when you’re at home. Also, check your blood glucose level as soon as possible after landing. Jet lag can make it hard to tell if you have very low or very high blood glucose.

Welcome

After a long flight, take it easy for a few days. Check your blood glucose often. If you take insulin, plan your activities so you can work in your insulin and meals. If you are more active than usual, your blood glucose could go too low. Take along snacks when hiking or sightseeing. Don’t assume you will be able to find food wherever you are.

No matter what kind of diabetes you have, it’s smart to watch what you eat and drink when traveling. Avoid tap water overseas. This includes ice cubes made from tap water. Ask for a list of ingredients for unfamiliar foods. Some foods may upset your stomach and hurt your diabetes control. But you will also find foods that give you a healthy taste of culture.

Wear comfortable shoes and never go barefoot. Check your feet every day. You should look for blisters, cuts, redness, swelling, and scratches. Get medical care at the first sign of infection or inflammation.

Go wherever your heart leads you. Just remember that you take your diabetes with you. Take your self-care along, too.