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August 14, 2002

Tight Control

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Question from Jacksonville, Florida, USA:

I know the DCCT looked at tight control, but what about normal A1cs? Are there any ongoing studies that look at people who have had diabetes for more than 15 years with A1cs in the normal range (4.0-6.0%) for that period for time? What do you think the complication rates would be for normalization around the clock, with a few highs but corrected shortly after? Do you think there is a difference in the rate of complications between a normal A1c of 6.0% and 7% (1% over the lab)?

Answer:

From: DTeam Staff

In the DCCT, we had some folks who did maintain their hemoglobin A1cs in the normal range, albeit not many. Their rate of hypoglycemia, especially severe hypoglycemia, was related directly to how low their A1cs were. Consequently, the recommendation was that folks try to achieve and or maintain the best blood glucose control possible, but to keep in mind that hypoglycemia is a definite risk with lower A1cs. For those with diabetes over about 15 years duration, much more hypoglycemia unawareness is seen, so that is scary if those with little or no awareness of lows are trying to keep their A1cs very low.

One other thought: when the DCCT ended nine years ago, we did not have some of the newer “designer insulins” No Humalog or NovoLog insulins were available then, which we have now to bring down blood glucose more rapidly. (We only had Regular insulin, which you had to give up to an hour before meals to bring down a high blood glucose ). We used quite a few insulin pumps in the DCCT, but they were not anywhere near as efficient or easy-to-use as those available now, and I think only about 30% of the experimental group were “consistently on pumps.” Now pump therapy is used more regularly for those trying to achieve the best control possible. So it is perhaps easier to maintain better blood glucose control now than 10 years ago. However the risk of hypoglycemia does remain.

LSF
Additional comments from Dr. Donough O’Brien:

As you quite rightly point out, the first definitive study that linked good control to a lesser expectation of complications was the DCCT. It has always been assumed since that complications could be reduced to a minimum with really meticulous control. However, I don’t know of any on-going long-term studies of people who seem to have managed to stay in really good control since diagnosis.

Such a project would raise some problems quite apart from the fact that such histories are rather few and far between, especially if they include the adolescent years. These relate primarily to the accuracy of the initial diagnosis. Fifteen years ago, antibody testing was less universal, and it is possible that such subjects could have type 1B diabetes, which is antibody negative, and in which, in about 50% of cases, there is significant restoration of islet cell function. They might also have been one of the variants of type 2 diabetes.

Precise diagnosis is really not important in management; but what is important is to persist with the occasional tests like microalbumin that hint at renal microvascular problems and also lead to successful early treatment.

DOB
Additional comments from Dr. Jim Lane:

Congratulations! You have already lived through the period of highest risk for diabetes-related kidney disease. The best information we have related to microvascular complications is keyed to theA1c. Neuropathy and retinopathy are more or less related to chronicity but the disease may have a slower onset. I don’t think we know completely what to say, other than you have lived through the highest risk period for nephropathy.

I am not aware of any large-scale studies looking at chronic type 1 diabetes with normal A1c levels. It piques my interest, however.

JTL
Additional comments from Dr. Stuart Brink:

The DCCT had many folks with excellent A1c levels in the 6’% range, and we know that the better the A1c, the lower the complications. Period. Eyes, kidneys, nervous system — and probably by inference, cardiovascular problems as well. So, keep up the good work.

If you want to look at exact references, you’ll need to get access to more than 100 articles from the DCCT. You may also try PubMed with key words DCCT to start.

SB