Robert S. Zimmerman, MD

In Reply: We appreciate Dr. Bell’s interest in and comments regarding our recent article. Dr. Bell contends that the DCCT¹ and UKPDS² studies should not be cited since the DCCT is a study of type 1 and not type 2 diabetic patients, and the UKPDS was performed in an era when statins were not available.

While we can appreciate his point of view, we disagree with his interpretation of the available data. These studies, and their respective observational follow-up reports,^3,4 provide evidence that early intervention may reduce cardiovascular risk, and that our approach to examining cardiovascular risk reduction in high-risk cardiovascular patients, as in ACCORD,⁵ ADVANCE,⁶ and VADT,⁷ may be short-sighted. There is an important difference between reducing long-term cardiovascular risk by treating younger and healthier patients with diabetes (type 1 or type 2) early in the disease course, before the development of complications (including cardiovascular disease), as was the case in DCCT and UKPDS, vs treating older patients with diabetes who have established cardiovascular disease or who have numerous risk factors substantially increasing their cardiovascular risk, as in ACCORD, ADVANCE, and VADT.

To his second point, that the UKPDS did not demonstrate cardiovascular risk reduction until after the 10-year follow-up when statins were probably utilized by the vast majority of patients, there would not have been a difference in cardiac events between treatment and control groups during this observational period if the statins were the cause of the reduced rate of cardiac events. The control and treatment groups would have had the same reduction in events. That was not the case. The finding of a lower risk of myocardial infarction at the completion of the follow-up period, despite ubiquitous statin use by both the treatment and control groups during this 10-year period, suggests another variable—ie, that the early differences in glycemic control achieved between the treatment and control groups during the UKPDS was responsible for the observed reduction in the risk of myocardial infarction.

In Reply: We appreciate Dr. Bell’s interest in and comments regarding our recent article. Dr. Bell contends that the DCCT¹ and UKPDS² studies should not be cited since the DCCT is a study of type 1 and not type 2 diabetic patients, and the UKPDS was performed in an era when statins were not available.

While we can appreciate his point of view, we disagree with his interpretation of the available data. These studies, and their respective observational follow-up reports,^3,4 provide evidence that early intervention may reduce cardiovascular risk, and that our approach to examining cardiovascular risk reduction in high-risk cardiovascular patients, as in ACCORD,⁵ ADVANCE,⁶ and VADT,⁷ may be short-sighted. There is an important difference between reducing long-term cardiovascular risk by treating younger and healthier patients with diabetes (type 1 or type 2) early in the disease course, before the development of complications (including cardiovascular disease), as was the case in DCCT and UKPDS, vs treating older patients with diabetes who have established cardiovascular disease or who have numerous risk factors substantially increasing their cardiovascular risk, as in ACCORD, ADVANCE, and VADT.

To his second point, that the UKPDS did not demonstrate cardiovascular risk reduction until after the 10-year follow-up when statins were probably utilized by the vast majority of patients, there would not have been a difference in cardiac events between treatment and control groups during this observational period if the statins were the cause of the reduced rate of cardiac events. The control and treatment groups would have had the same reduction in events. That was not the case. The finding of a lower risk of myocardial infarction at the completion of the follow-up period, despite ubiquitous statin use by both the treatment and control groups during this 10-year period, suggests another variable—ie, that the early differences in glycemic control achieved between the treatment and control groups during the UKPDS was responsible for the observed reduction in the risk of myocardial infarction.

In Reply: We appreciate Dr. Bell’s interest in and comments regarding our recent article. Dr. Bell contends that the DCCT¹ and UKPDS² studies should not be cited since the DCCT is a study of type 1 and not type 2 diabetic patients, and the UKPDS was performed in an era when statins were not available.

While we can appreciate his point of view, we disagree with his interpretation of the available data. These studies, and their respective observational follow-up reports,^3,4 provide evidence that early intervention may reduce cardiovascular risk, and that our approach to examining cardiovascular risk reduction in high-risk cardiovascular patients, as in ACCORD,⁵ ADVANCE,⁶ and VADT,⁷ may be short-sighted. There is an important difference between reducing long-term cardiovascular risk by treating younger and healthier patients with diabetes (type 1 or type 2) early in the disease course, before the development of complications (including cardiovascular disease), as was the case in DCCT and UKPDS, vs treating older patients with diabetes who have established cardiovascular disease or who have numerous risk factors substantially increasing their cardiovascular risk, as in ACCORD, ADVANCE, and VADT.

To his second point, that the UKPDS did not demonstrate cardiovascular risk reduction until after the 10-year follow-up when statins were probably utilized by the vast majority of patients, there would not have been a difference in cardiac events between treatment and control groups during this observational period if the statins were the cause of the reduced rate of cardiac events. The control and treatment groups would have had the same reduction in events. That was not the case. The finding of a lower risk of myocardial infarction at the completion of the follow-up period, despite ubiquitous statin use by both the treatment and control groups during this 10-year period, suggests another variable—ie, that the early differences in glycemic control achieved between the treatment and control groups during the UKPDS was responsible for the observed reduction in the risk of myocardial infarction.