Abstract
Jellinger, Lebovitz, and Davidson (1), writing on behalf of the American College of Endocrinology/American Association of Clinical Endocrinologists (ACE/AACE) Outpatient Glycemic Control Implementation Task Force, challenge the consensus treatment algorithm of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (2). I will attempt to answer each of their objections. First, I will address the statement that the therapeutic A1C target should be <6.5% rather than <7.0%. The discussion of this point needs to be separated into microvascular and macrovascular outcomes. Regarding microvascular disease, there have been five studies in over 2,000 type 1 (3–5) and type 2 (6,7) diabetic patients demonstrating that there was virtually no development or progression of retinopathy and nephropathy over 6–9 years if mean A1C levels are maintained at <7.0%. In two of these studies (3,6), an intervention that lowered glycemia resulted in much less retinopathy and neuropathy, proving a causative relationship between control and improved outcomes. Regarding macrovascular disease, there is an association with glycemia defined by oral glucose tolerance testing that extends down into the midnormal range (8). Regarding glycemia at more than one point in time, there are significant ∼2.5-fold increases in clinical cardiac events in individuals with A1C levels >5.0% in one study (9) or 4.6% in another (10) over 4 or 8–10 years, respectively. However, in addition to the impossibility of reducing A1C levels to these values, association must not be confused with causation. One of the only things I remember from the biostatistics course in the first year of medical …
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