Lower glucose does not mean better for diabetics

SUNDAY JUNE 8, 2008 (foodconsumer.org) -- A trial showed that people with type 2 diabetes who received intensive treatment aiming at reducing their blood glucose levels to normal were at a much higher risk of death than those who were treated with a standard therapy, which aims to control the level above the normal.

The intensive treatment aimed to lower glycated hemoglobin levels to normal, 6% or even lower while the standard therapy is to lower the protein to about 7.5% ranging from 7.0% to 7.9%. The glycated hemoglobin level is the measurement doctors use to assess diabetics' blood glucose levels.

Previous epidemiologic studies have found there is an association between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. But it remains unknown whether lowering blood glucose would help reduce the risk.

The trial known as Action to Control Cardiovascular Risk in Diabetes (ACCORD) was intended to examine if lowering glucose levels to the normal range in the diabetes patients would reduce their risk of cardiovascular events such as heart attack, stroke or death. 

The trial involved 10,251 patients at an average age of 62.2 years with a median glycated hemoglobin level of 8.1%. Of the patients, 38 percent were women and 35 percent had had a previous cardiovascular event prior to entering the study.

The researchers followed the diabetics for a mean of 3.5 years for incidence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.

Within a year, both groups achieved the targeted glycated hemoglobin levels of 6.4% in the intensive treatment group and 7.5% in the standard therapy group.

During follow-up, 352 patients in the intensive-treatment group experienced nonfatal cardiovascular events compared to 371 in the standard group.

However, of those intensively treated, 257 patients died compared to 203 in the group treated with standard therapy. More of those who received intensive treatment gained more than 10 kg body weight and required assistance because of hyperglycemia.

The researchers conclude that "As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes."

The trial, funded by the National Heart, Lung, and Blood Institute and conducted by researchers from the U.S. government and Canadian organizations, was published in the New England Journal of Medicine at www.nejm.org June 6, 2008 (10.1056/NEJMoa0802743).

 Another study led by Australian researchers and also published in the same issue of the journal showed a different outcome by lowering glucose levels in diabetes patients.

That study, known as The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, found when glycated hemoglobin levels were reduced to 6.5 percent, a level below the standard target, resulted in a 10 percent reduction in the combined outcome of major macrovascular and microvascular events, which was primarily due to a 21% relative reduction in nephropathy.

However, between the two groups, there was no significant difference in incidence of cardiovascular events including death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

The Australian trial was as sizable as ACCORD, including 11,140 diabetes patients, and meant to determine the difference the standard glucose control and intensive glucose control could make in the risks of major macrovascular events including death from cardiovascular cause, nonfatal myocardial infarction or nonfatal stroke and major microvascular events including new or worsening nephropathy or retinopathy.

The trial lasted 5 years. Glycated hemoglobin level was lowered to 6.5% in the intensive control group and to 7.3% in the standard control group.

Incidence of combined major macrovascular and microvacular events were 18.1 vs. 20% in the intensive group and standard group respectively. No significant effects of the type of glucose control were observed on death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in diabetes patients.

Both studies came to an agreement that lowering glucose levels near normal did not reduce cardiovascular risk during a 3 to 5 year period although the Australian trial showed the intensive treatment may result in some benefits.

For more information, read

Effects of Intensive Glucose Lowering in Type 2 Diabetes

Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes

Related Editorial: Intensive Glycemic Control in the ACCORD and ADVANCE Trials

Related Editorial: Glycemic Targets and Cardiovascular Disease

By Sue Mueller
Jun 8, 2008 - 11:19:33 AM