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The Role of Glycemia Management in the Prevention of Cardiovascular Disease—Starting Over?

David M. Nathan, MD
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From Massachusetts General Hospital Diabetes Center, Boston, MA 02114.

Potential Conflicts of Interest: None disclosed.

Requests for Single Reprints: David M. Nathan, MD, Massachusetts General Hospital Diabetes Center, 50 Staniford Street, Boston, MA 02114; e-mail, dnathan@partners.org.

Ann Intern Med. 2009;151(12):888-889. doi:10.7326/0003-4819-151-12-200912150-00010
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The DCCT (Diabetes Control and Complications Trial) for type 1 diabetes (1) and the UKPDS (United Kingdom Prospective Diabetes Study) for type 2 diabetes (2) seemed to lay to rest the contentious debate over the relationship between glycemic control and the long-term complications of diabetes mellitus. These randomized trials of intensive therapy to achieve near-normal glucose control established the benefits of intensive therapy over conventional (at the time) therapy on the microvascular and neurologic complications that epidemiologic studies had shown to be associated with the level of chronic glycemia (34). Neither trial established that intensive therapy reduced cardiovascular disease (CVD), a major cause of morbidity and mortality in diabetes, possibly because of the low number of events (12, 5). Subsequent observational follow-up data demonstrated 57% and 15% reductions in major CVD events in the DCCT and UKPDS, respectively, on the basis of intention-to-treat analyses of original treatment assignment (67). The more profound effect of intensive therapy in the DCCT than in the UKPDS cohort was probably the result of greater separation in hemoglobin A1c (HbA1c) levels in the DCCT than in the UKPDS and the more complex CVD risk background of type 2 diabetes, with its associated hypertension, dyslipidemia, obesity, and older age (8). The rate of CVD was about 4-fold higher in the UKPDS population than in the DCCT population, both with about 25 years of diabetes duration (67).

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