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Published on: June 11, 2012
Glycemic targets for patients with type 2 diabetes mellitus
Ole-Petter R Hamnvik1, Graham T McMahon
1Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Abstract:
Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins.
Insights
Intensive glucose control in diabetes trials showed mixed results, with one study noting increased mortality. Managing cardiovascular disease risk requires both glycemic control and addressing other risk factors like hypertension and lifestyle.
Area of Science:
- Endocrinology
- Cardiology
- Clinical Trials
Background:
- Cardiovascular disease (CVD) is the leading cause of death in diabetic patients.
- Large trials like ACCORD, ADVANCE, and VADT investigated intensive versus standard glycemic control in high-risk diabetics.
- The ACCORD trial's intensive glycemic control arm was halted due to increased mortality.
Purpose of the Study:
- To evaluate the impact of intensive glycemic control on cardiovascular outcomes in diabetic patients.
- To explore reasons for conflicting results across major diabetes trials regarding CVD risk reduction.
Main Methods:
- Randomized controlled trials comparing intensive and standard glycemic control strategies.
- Analysis of all-cause and cardiovascular mortality in high-risk diabetic populations.
- Post hoc analyses to investigate potential causes for observed mortality differences.
Main Results:
- The Action To Control Cardiovascular Risk in Diabetes (ACCORD) trial found increased all-cause and cardiovascular mortality with intensive treatment.
- The ADVANCE and Veterans Affairs Diabetes Trial (VADT) did not replicate these increased mortality findings.
- Explanations for ACCORD's results, such as hypoglycemia or medication effects, were not validated.
Conclusions:
- The cause of increased mortality in the ACCORD trial's intensive arm remains unclear.
- Subgroup analyses suggest potential benefits of tight glycemic control for patients with better baseline diabetes control or no prior CVD.
- Reducing macrovascular risk in diabetes necessitates comprehensive management of glycemic and non-glycemic factors, including hypertension, lipids, and lifestyle, alongside preventative medications.
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