Volume 1, Number 1: Spring Equinox, 1999

New Frontiers in Diabetes Research - BC Endocrine Research Foundation

Dr. Keith Dawson MD, PhD, FRCPC

Introduction

In the past year there have been dramatic new findings from clinical research in Diabetes, which will change the way clinical care will be delivered in the next five years. While basic understanding of the disease – that is, what causes diabetes, including genetic, metabolic and environmental causes, is rapidly expanding, there does not appear to be any cure for the disease available or on the horizon.

This is of some concern for Canadians are really not aware of how serious and pervasive this disease is. It affects about 1.5 million Canadians, and an additional 750,000 Canadians have the disease and don’t know they have it. Once you get the disease, you cannot “cure” it. You can treat it, simply with diet and exercise or eventually with pills, but it does not go away! You have it for the rest of your life. You are living with the constant concern that you may develop loss of eyesight, loss of sensation in your extremities, kidney disease and of course a 2 to 5-fold risk of heart disease and stroke. Because this is not a simple health care problem in Canada, but a serious one that is increasing in incidence every year, the new research on treating the disease is very hopeful and stimulating.

What are some of these new findings?

The American Diabetes Association as well as the World Health Organization and the Canadian Diabetes Association have studied the disease and come out with new criteria for its diagnosis and new recommendations as to whom should be tested and when. These new Canadian Guidelines were published in October 1998. What are some of the more important new recommendations?

First, everyone over the age of 45 should have a single blood test for the presence of diabetes. Those with one of the following high risk factors should be tested even before age 45. These risk factors include high blood pressure or other cardiovascular disease, a family history of diabetes, a history of diabetes during pregnancy, abnormal cholesterol and other lipids in the blood, and obesity.

Secondly, the level at which diabetes will be diagnosed will be lower. Whereas the normal fasting blood glucose does not exceed 6.1 mmols/L, we formerly diagnosed diabetes only when the level was higher than 7.8 mmols/L. We now realize that level was too high and too many with diabetes were not being diagnosed. The critical level was therefore reduced to less than 7.0 mmols/L. Even so, up to 56% of people with mild diabetes will be missed by this new standard. Many, however, will now be recognized earlier, and treatment provided. This is of great importance when we realize that 50% of those diagnosed with diabetes already have at least one complication of the disease. So earlier diagnosis will, we hope, prevent these problems.

Thirdly, the new guidelines emphasize that the treatment of diabetes must be much more aggressive than most physicians realize. It will be necessary in the future to bring the blood sugar down much nearer to normal than currently emphasized. The goal level of fasting blood glucose is to be less than 7.5 mmols/L. Only by achieving this can we avoid complications from developing in the person with diabetes.

At almost the same time as these new guidelines were published, the largest single study on the treatment of type 2 diabetes – the diabetes that usually begins after the age of 30 – was published [1, 2]. Called the United Kingdom Prospective Diabetes Study, this study enrolled about 5000 people and followed them with various treatment regimens over 15 years. This study proved some things that were well known, and taught us some things completely new. In the well known group, it was shown that type II diabetes is a very hard disease to treat, and that it is very hard to get people to change their lifestyle, eating habits, exercise habits, and medications on a long-term basis. It is not hard to make such changes over the short term, but it is nearly impossible under conventional treatment schemes to change behaviour permanently.

How was this shown?

The best treatment when provided by family physicians who are specifically advised how and what to do, is only able to slow the downward spiral and is not able to prevent heart attacks and major complications to a great degree. Thus, optimal treatment only reduced overall major complications by 12% compared to those treated in a casual fashion. While some microvascular complications such as progression of eye disease were reduced (25%), the known high incidence of major complications was not significantly reduced in those treated in the “intense” manner. The findings are much more encouraging if one looks at all those patients who successfully lowered their glucose levels. When viewed this way, from the point of view of an epidemiologist, it was seen that for every 1% reduction in the Hemoglobin A1c level (the standard test indicating blood glucose control) there was a 21% reduction in diabetes complications. With that information, it becomes clear that we must find a way to lower the blood glucose levels in all people with diabetes, and to maintain that low level over the long term.

What were some of the unexpected findings?

In the first place, it was clearly shown that diet and exercise alone is very ineffective over the long term unless other treatments are added. Only 3% of the entire group were able to hold glucose levels down to the necessary degree using diet alone.

Secondly, it was shown that, with the medication we currently have available, we are able to lower glucose levels adequately but not by using one medication alone. While one medication may work for a few years, most people will need a second medication within five years, and a third medication within ten years. Insulin will have to be given in much higher doses than was used in this large trial, in order to achieve long-term success.

Thirdly, some of the newer medications will have to be used if success is to be achieved. While three classes of drugs were used in this large study, sulfonylurea agents (including glyburide), metformin, and insulin, other agents such as thiazolidinediones will be required in some people. New insulin forms such as Lispro insulin (Humalog) will have a needed role. Currently neither of these is approved for use in the pharmacare program in British Columbia due principally to their cost. We will have to lobby the government to approve such medications to enhance our ability to treat all people to the optimal level.

Fourthly, one of the most impressive findings in this research was that blood pressure control turned out to be even more important than blood glucose control in preventing the complications of type 2 diabetes. Formerly we knew that the goal level of blood pressure control was less than 140/90, but this study showed major reductions in heart attacks, strokes and eye and kidney complications were achieved if the blood pressure was reduced to an average of 144/82. To effect this, once again several medications were required. The unfortunate truth is that prevention of the complications of diabetes will require polypharmacy both in glucose lowering and blood pressure lowering drugs. On the positive side, it was shown that successful outcomes can be achieved if we can encourage the person with diabetes and the entire medical team to persist until goal levels are reached – when this is done, complications will be avoided.

There were many detailed findings in these studies, which cannot be reported here. They are findings that must be transmitted not only to physicians and nurses treating people with diabetes, but more importantly to the people who have the disease. Patients can participate in their own care, understand why it is vital that they understand the importance of achieving these goals, and how to do it.

Dr. Keith Dawson is an active researcher and educator in diabetes and maintains a busy practice treating individuals with diabetes.

References

  1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) The Lancet, 1998, Vol. 352; pg. 837-853.
  2. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) The Lancet, 1998, Vol. 352; pg. 853-865.

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Email: aleta.allen@vch.ca
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President: Dr. Marshall Dahl
Vice-President: Dr. David M. Thompson

Board Members: Dr. Keith Dawson, Dr. Jason Kong, Dr. Ehud Ur, Dr. Jerilynn Prior, Dr. Tom Elliott, Dr. Breay Paty, Dr. Sandra Sirrs

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Administrator: Aleta Allen