Intensive glucose control in type 2 diabetes reduces cardiovascular disease, but not cardiovascular or all-cause mortality, and increases risk of severe hypoglycaemia
- Deborah Chyun
Florence S. Downs Director, Program in Nursing Research and Theory Development, College of Nursing, New York University, 726 Broadway, New York, NY 10003, USA;
Previous studies—the Diabetes Control and Complications Trial1 in type 1 diabetes and the United Kingdom Prospective Diabetes Study2 in type 2 diabetes—have clearly demonstrated the benefits of intensive glucose control for the prevention of the microvascular complications of diabetes (neuropathy, nephropathy and retinopathy). In addition, long-term follow-up of the younger subjects with type 1 diabetes who were enrolled in the Diabetes Control and Complications Trial demonstrated that those in the intensive arm had a reduced risk of developing cardiovascular disease (CVD), long after the initial phase of the study.3 However, the effects of intensive glucose lowering on CVD outcomes in type 2 dia betes have been unclear. Three contemporary trials—Action in Diabetes and Vascular Disease,4 the Veterans Affairs Diabetes Trial,5 and Action to Control Cardiovascular Disease in Diabetes6—were designed to answer this question. There was considerable anticipation in the dia betes community that these trials would provide evidence to support the widely held belief that intensive glucose control could also lower the risk of CVD, which remains the leading cause of death in individuals with diabetes. However, the findings from all three trials did not support the hypothesis that intensive glucose lowering had a bene fit on CVD events, and, importantly, unexpectedly high mortality in subjects randomised to receive intensive glucose control (HbA1c to <6%) in the Action to Control Cardiovascular Disease in Diabetes trial highlighted the potential adverse effects of intensive treatment and attendant hypoglycaemia.
The meta-analysis by Kelly and colleagues is an important attempt to clarify the results of these glucoselowering trials (HbA1c ≤6.5%), given the increasing prevalence of type 2 diabetes, the elevated risk of CVD in this population and the known benefits of glucose control on microvascular disease. The well-constructed analysis demonstrated that intensive glucose control reduced the risk of CVD (relative risk (RR) 0.90, 95% CI 0.83 to 0.98) but not CVD-related death (RR 0.97, 95% CI 0.76 to 1.24), while increasing the risk of severe hypoglycaemia (RR 2.03, 95% CI 1.46 to 2.81). The distinction between CVD and CVD-related death is an important one, as are the subject characteristics that may have contributed to the lack of reduction in mortality. A substantial number of subjects in these three trials had pre-established CVD at study entry (32–40%) and an adverse CVD risk factor profile, along with a long duration of diabetes (mean 7.9–11.5 years). Prevention of non-fatal myocardial infarction identified in this meta-analysis is therefore an important finding. Equally important is the elevated risk of hypoglycaemia.
A recent scientific statement has attempted to place these findings into perspective and serve as a guide for clinical practice.7 The authors remind us of the importance of multifactorial risk reduction and the substantial benefits of blood pressure lowering, which were also demonstrated in the UK Prospective Diabetes Study,2 along with statin and aspirin therapy. They conclude that providers should maintain an HbA1c target of <7%, as well as attempting to control other CVD risk factors. In addition, individualisation of glycemic goals, particularly in those with known CVD or other diabetes-related complications and a longer disease duration, is needed. Further intensification of glucose control may be appropriate for other individuals, but hypoglycaemia should be avoided. Nursing has an important role in the prevention and management of CVD in individuals with diabetes. It is critical that prevention, prompt identification and management of hypoglycaemia be highlighted as important components of diabetes selfmanagement education. Given the hazards of hypoglycaemia in those with long-standing diabetes and pre-existing CVD, as well as the long-terms benefits of intensive glucose control when diabetes is recognised and treated early in its course, screening for diabetes in high-risk individuals and early achievement of glucose control are critical.
Competing interests None.