Treating Your Numbers in Type 2 Diabetes—Is Lower Better?

Type II diabetes, the kind that most people have, is characterized by two abnormal numbers. The first is an elevated blood sugar and the second is an elevated Hemoglobin A1c.

There are two types of damage in type II diabetes: Microvascular damage and macrovascular damage.

Microvascular damage means damage to the small blood vessels, the microscopic blood vessels, and is evidenced by kidney damage, damage to the retina, and to the nerves. The second kind of damage is macrovascular damage or damage to the large blood vessels which results in an increased risk of heart attack, stroke, peripheral vascular disease, and death.

The higher the two measures of type II diabetes, the blood sugars and the Hemoglobin A1c, the greater the risk of microvascular disease and of macrovascular disease more commonly called cardiovascular disease. And so we’ve always assumed that the lower we can get those two numbers, better the patients will do.

And for microvascular disease (kidney problems, eye problems and nerve problems) the studies Do show that lower is better. However, the vast majority of increased death due to type II diabetes is caused by macrovascular disease (cardiovascular disease). And we’ve always assumed that as we lower the blood sugars and the Hemoglobin A1cs, we are also lowering the risk of cardiovascular disease and death. Recent studies have clearly call that into question.

When a plasma glucose level is greater than 125 mg per deciliter after at least an eight hour fast on two separate occasions then we diagnose diabetes.

When we follow diabetes we measure fasting blood sugars in the morning, blood sugars before meals, and sometimes blood sugars two hours after meals. The higher the numbers, the worse is the diabetes and the more likely are complications.

The second number we measure to follow diabetes is the Hemoglobin A1c.The Hemoglobin A1c is a measure of the percentage of hemoglobin molecules that have glucose molecules attached to them. The higher the average blood sugar throughout a three-month period, the higher will be the Hemoglobin A1c percentage.

The American diabetes Association has defined a normal as less than 6.5%. A Hemoglobin A1c of 7% is equivalent to an average blood sugar of 154 mg per deciliter over three months. A Hemoglobin A1c of 8% corresponds to a three month average of 183 mg per deciliter. AndA 9% Hemoglobin A1c corresponds to an average three-month blood sugar of 212 mg per deciliter!

Three recent studies have been performed to see if lowering the Hemoglobin A1c, which means lowering the average blood sugar, lowers the risk of cardiovascular disease. In other words, does more intensive treatment of type II diabetes (meaning more medicines and more blood sugar checks) lower the risk of cardiovascular disease and death as compared to less intensive treatment.

Again the assumption is always been that the lower the numbers, the lower the risk of cardiovascular disease and death. That’s why the American diabetes Association recommends a treatment goal for patients with type II diabetes of the Hemoglobin A1c of less than 7% for most adults.

Three new studies have called this assumption into question. These studies were ACCORD, ADVANCE (this link is to a summary article in Diabetes Care), and VADT.

In the ACCORD study, 10,251 patients were randomized to intensive therapy (lots of blood sugar lowering medicine), with the goal of getting the Hemoglobin A1c to less than 6.0% or randomized to a standard Hemoglobin A1c goal of 7.0 to 7.9%. The patients coming into the study had an average Hemoglobin A1c of 8.1% and those placed in the intensive therapy group got down to an average of 6.4% and those placed into standard therapy group achieved an average Hemoglobin A1c of 7.5%.

The ACCORD study was stopped early because the death rate in the intensive therapy arm (more medicines) was significantly higher than in the standard therapy treatment group (a death rate of 1.41% per year in the intensive therapy group versus 1.14% per year for standard therapy).

So, in the ACCORD study, intensive effort to lower the blood sugars and to lower the Hemoglobin A1c measures did not lower the death rate. In fact, the death rate was higher in patients treated more intensively than in the standard therapy group. Lower clearly was not better in this trial.

The ADVANCE trial and the VADT trial were similar to the ACCORD trial and they showed no lowering of the overall death rate with intensive therapy, but at least there was no increase in the death rate with intensive therapy as happened in the ACCORD trial.

So there comes a point at which lower (lower blood sugars and lower Hemoglobin A1cs) is not always better.

Although intensive therapy not decrease the overall death rate, unfortunately it does decrease significantly patients quality of life according to the editorial  Intensified glucose lowering in type 2 diabetes: time for a reappraisalDiabetologia October 2010, Volume 53, Issue 10, pp 2079-2085.

And the editorial’s authors conclude that “Good glucose control does indeed offer protection against microvascular complications, cataracts and neuropathy, but the added benefits of an HbA1c of 7%, as against 8%, diminish with age and life expectancy. In such instances efforts and resources would be better directed to those with higher levels of HbA1c, who have much more to gain from attention to their glucose control. Each individual should indeed be encouraged to achieve the best possible compromise between glucose control and vascular risk, but fully informed consent should be the prelude to intensified therapy. This is not achieved when benefits are grossly overestimated, or when trials are presented in terms of relative risk reductions—‘25% fewer heart attacks’.”

Bottom line is making a person miserable (with lots of daily blood tests and lots of different medicines and lots of daily insulin shots) trying to get the hemoglobin A1c below 7% may not make sense.

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