Originally published September 10 2008
Oral Glucose Medications Increase Mortality in Type 2 Diabetes Patients
by Helmut Beierbeck
(NaturalNews) Poor blood glucose control puts diabetics at increased risk for cardiovascular disease (CVD). Every percentage point increase in glycated hemoglobin levels (a blood glucose marker) above normal values raises the relative CVD risk by roughly 20% (1). The percentage of glycated hemoglobin, more specifically hemoglobin A1c (HbA1c), is a measure of average blood glucose levels over the previous 2 to 3 months. Healthy HbA1c levels range from 4% to 6%.
Although this positive correlation between blood glucose levels and CVD had been known, no clinical trials had ever tested the effect of lowering glucose levels on cardiovascular risk. Two major clinical trials, the ACCORD and ADVANCE trials, were therefore undertaken to determine whether intensive pharmacological intervention to lower HbA1c levels in type 2 diabetics reduced the risk of major cardiovascular events.
The ACCORD and ADVANCE trials had a number of features in common:
* Both studies were large-scale trials, each enrolling more than 10,000 patients. The ACCORD trial recruited patients from the U.S. and Canada. The ADVANCE trial was spread over more than 200 medical centers in twenty countries around the world.
* Both studies enrolled patients who were middle-aged or older, with type 2 diabetes and either established cardiovascular disease or cardiovascular risk factors.
* In both studies, half the patients received intensive care with aggressive pharmacological intervention. The comparison group received standard therapy.
* In addition to oral glucose lowering drugs, many patients in both trials also received medications to control blood pressure, cholesterol levels and blood clotting.
* The primary difference between the two studies was the choice of oral diabetes drugs. The ACCORD trial used mainly thiazolidinediones. Patients in the ADVANCE study were given the sulfonylurea drug gliclazide, plus insulin or thiazolidinediones as needed to achieve target HbA1c levels.
The results of these two clinical trials were published in the June 12, 2008 issue of the New England Journal of Medicine, together with a couple of commentaries (2-5). Both trials succeeded in lowering glucose levels. The final average HbA1c values were 6.5% and 7.5% with the intensive and standard regimen, respectively.
However, both trials clearly failed in their primary objective, to reduce the number of deaths from cardiovascular disease. The ADVANCE trial found no drop in CVD, but confirmed that lowering glucose levels decreases the risk of microvascular complications, specifically renal failure and retinopathy (3). In the ACCORD trial the death rate actually increased in the intensive treatment group; the trial was halted and patients were switched from intensive to standard therapy (2).
These results come on the heels of a May 21, 2007 warning by the FDA that another thiazolidinedione drug, Avandia (rosiglitazone), increases the risk of major cardiovascular events:
"Recently, the manufacturer of Avandia (GlaxoSmithKline) provided FDA with a pooled analysis (meta analysis) of 42 randomized, controlled clinical trials in which Avandia was compared to either placebo or other anti-diabetic therapies in patients with type 2 diabetes. The pooled analysis suggested that patients receiving short-term (most studies were 6 months duration) treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy. These data, if confirmed, would be of significant concern since patients with diabetes are already at an increased risk of heart disease." (6)
The failure of these trials to reduce cardiovascular risk by pharmacological means does not disprove a connection between glucose levels and cardiovascular disease:
"Neither the ADVANCE trial nor the ACCORD trial undermines the importance of meeting the current guidelines for care, and they should not be interpreted as diminishing the importance of glycemic control." (4)
The ACCORD and ADVANCE trials failed because of the chosen methodologies. The pharmaceutical cocktail used in the two studies either didn't work or made matters worse:
"As clearly stated by the investigators in the ACCORD trial, the potential existed for undetected adverse effects owing to an increased number of changes in drug regimens and an increased use of multiple drug classes and at increased doses." (5)
Glycemic control is achievable by lifestyle and dietary changes, something that was apparently not emphasized in either trial. Even mainstream medicine acknowledges the effectiveness of diet modifications in preventing and managing diabetes:
"But this epidemic [of CVD with rising blood glucose levels] is not inevitable -- it may be thwarted if we take action now. We know that lifestyle changes can dramatically reduce the incidence of diabetes and slow the hemoglobin A1c increase in both diabetic and nondiabetic individuals. Broadly adopted lifestyle changes should therefore reduce diabetes-related eye, kidney, and nerve disease. Regardless of whether these lifestyle changes are ultimately proven to reduce cardiovascular disease in our society, public health approaches to facilitate them urgently need to be implemented. Structural changes to our society that reduce caloric intake and increase physical activity today will lower hemoglobin A1c levels and reduce society's rates of diabetes, the consequences of diabetes, and possibly cardiovascular disease tomorrow." (1)
"People with diabetes have the same nutritional needs as anyone else. Along with exercise and medications (insulin or oral diabetic pills), nutrition is important for good diabetes control. By eating well-balanced meals in the correct amounts, you can keep your blood glucose levels as close to normal (non-diabetic level) as possible." (7)
Type 2 diabetes is considered a lifestyle disease, and it can be prevented and even reversed through proper diet and exercise. Follow a low glycemic eating plan if you don't want to become a guinea pig and a source of income for the pharmaceutical industry.
1. Gerstein HC. Glycosylated hemoglobin: Finally ready for prime time as a cardiovascular risk factor. Ann Intern Med 2004;141:475-476. (http://www.annals.org/cgi/reprint/141/6/475....)
2. Effects of intensive glucose lowering in type 2 diabetes. The action to Control cardiovascular risk in diabetes study group. N Engl J Med 2008;358(24):2545-2559. (http://content.nejm.org/cgi/reprint/358/24/2...)
3. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The ADVANCE collaborative group. N Engl J Med 2008;358(24):2560-2572.
4. Dluhy RG et al. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med 2008;358(24):2630-2633. (http://content.nejm.org/cgi/reprint/358/24/2...)
5. Cefalu WT. Glycemic targets and cardiovascular disease. N Engl J Med 2008;358(24)2633-2635. (http://content.nejm.org/cgi/reprint/358/24/2...)
6. FDA issues safety alert on Avandia, May 21, 2007. (http://www.fda.gov/bbs/topics/NEWS/2007/NEW0...)
7. Nutrition & Recipes. American Diabetes Association. (http://www.diabetes.org/nutrition-and-recipe...)
About the authorHelmut Beierbeck has a science background and a strong interest in all scientific aspects of health, nutrition, medicine, weight loss, or any other topic related to wellness. You can follow his ruminations on his blog http://healthcomments.info and leave comments on this or any other health-related topic.
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