David Toth, MD
TCOYD Newsletter, Vol. 28, 2009

“ACCORD Trial A Complete Bust.”
“Tight Glucose Control? According to ACCORD, Maybe Not.”
“Diabetes Control Shows No Benefit in ADVANCE.”

The headlines are enough to cause your heart to pound with uncertainty. Even many health-care professionals don’t know what to do about some of the latest studies. For those of us who deal with diabetes on a daily basis, in our personal lives, profession, or both, we always thought that lowering blood sugars as much as possible would translate into fewer complications and better outcomes. However, two large trials published in the past year, ACCORD and ADVANCE , make some people question the validity of this.

Decreasing Microvascular Complications

Both of these trials were designed to study the effect of very tight blood sugar control on prevention of heart disease. We know that tight blood sugar control is beneficial for some things already, but no one has proven that going below our current target for blood sugar control is more effective at preventing heart attacks and heart disease. (The ADA recommends A1c under 7% and the American Association of Clinical Endocrinologists suggests that it be below 6.5%.) Blindness, kidney disease, and amputations are collectively known as microvascular complications, since it is damage to the very small blood vessels in our body that lead to these. Diabetes is still the number one cause of blindness, the number one cause of end-stage kidney disease that leads to dialysis, and the number one cause of amputations that didn’t occur because of an accident or trauma. Microvascular complications are frightening in and of themselves, but, moreover, someone who has one is more likely to have a shorter life span than someone who doesn’t. Older studies like the UKPDS study for type 2 diabetes, as well as the DCCT in people with type 1 diabetes both clearly showed that there is a decreased risk of microvascular complications with lower A1c levels. In addition, the risk keeps going down further and further the lower that you decrease the A1c level.

Heart Disease

But what of heart disease? Well, ADVANCE showed no benefit in reaching an A1c below 6.5% in prevention of heart disease. Perhaps more disturbing on the surface, the ACCORD study showed that there was actually an increased risk of heart death in those patients treated with tight glucose control (their aim was to get the A1c level under 6%). So, again pointing to the headlines at the start of this story, a lot of people decided that this was it— tight blood sugar control is not needed. For years, providers have been telling their patients to get their sugars lower to prevent heart disease. If the goal of controlling diabetes is to reduce risks that will lead to complications such as heart attack, heart disease, stroke, and the like, how is one supposed to control glucose levels?

Healthy Heart

Let’s start with the easy things, namely cholesterol and blood pressure. There have been numerous studies showing remarkable benefit from using statin medications (simvastatin, atorvastatin, rousvestatin, and the like) to get the LDL (bad) cholesterol below 100 (and perhaps even closer to 70). Studies have also shown that lowering triglyceride levels with medications or raising the HDL (good) cholesterol with exercise and weight loss will also go very far in terms of preventing heart disease and stroke. Studies have also shown that the most popular blood pressure medications will reduce the risk of heart disease, provided that blood pressure is probably kept below 130/80. And how many of us are taking an aspirin a day to help prevent heart disease? In the ADVANCE study, only half of the participants took daily aspirin, and only half were on statin medication for cholesterol, which may have led to more heart disease than should have been expected.

So what about blood sugar? One of the largest studies of type 2 diabetes, the UKPDS, showed a reduced rate of heart attack and death in newly diagnosed people who were taking metformin for their diabetes. This benefit was seen even ten years after the study ended.

During the ten years of the study, there also was a trend toward a decreased risk of heart disease that directly correlated with a lower A1c level. This trend was never proven to be statistically significant, but most people figured that the numbers were headed in the right direction, at least. The UKPDS also suggests that the sooner a newly diagnosed person is in control of their blood sugars, the better the long term outlook for decreasing risk of heart disease.

What then, do we make of the headlines? First of all (and this is really important!) having uncontrolled high blood sugars will raise your risk for heart disease and stroke. When the researchers in the ACCORD trial drove the blood sugars down, it was with an increased rate of hypoglycemia, and that is the likely key. One way the body responds to hypoglycemia is by releasing the adrenaline hormones (epinephrine and norepinephrine). These hormones give the symptoms of palpitations, sweats, tremor, and agitation. In doing so they also increase the blood pressure and the work the heart does in pumping blood. The more time someone spends in hypoglycemia, the more work the heart has to perform. It is perhaps this increased work that causes the damage and makes the heart more susceptible to heart disease.

Having said all that, how do you prevent heart diseas? Well, first and foremost, make sure that blood presure and cholesterol are appropriately controlled with the proper medications, and that you are taking an aspirin daily if your doctor thinks that's safe. In terms of blood sugars, ask your doctor about the medication you are taking and its risk of giving you low blood sugars. Also make sure that you are checking your blod sugards often enough to know when you are too high and if you are at risk of having too much hypoglycemia. With that information, you and your doctor can decide on the best agents to use for blood sugar control, and how reasonably low your blood sugars can be. With all the tools we have at our disposal, we are well equipped to help prevent all of the complications of diabetes better than we every have been before.