to the editor: I am disappointed that this article does not question the American Diabetes Association's recommendation to normalize blood glucose, aiming for an A1C level of less than 7 percent.1 The article does not mention that in randomized controlled trials, this A1C goal was associated with increased mortality (ACCORD trial),2 nor does it mention that other trials have found little or no benefit to normalization of blood glucose (UKPDS,3 ADVANCE,4 trials). Family physicians care about the entire patient, not just their insulin levels, pancreatic islet beta cell function, and glycosylated hemoglobin measurements. Glucose normalization interventions place tremendous burdens upon our patients and are not supported by the evidence. Time and money spent chasing elusive blood glucose targets could be better applied toward interventions that have proven benefits.
Readers of American Family Physician (AFP) can go virtually anywhere else to listen to the disease-oriented, non-evidence-based, sugar-obsessed mantra of diabetes specialists. I read AFP to hear the voice of our profession, based on our whole-patient approach, which aligns with our patients' values.
in reply: In our article, we used the clinical practice guidelines from the American Diabetes Association1 when recommending that the A1C goal be less than 7 percent without risking significant hypoglycemia for patients with diabetes mellitus. These guidelines are published annually and are based on a review of all available evidence. The most recent version continues to support an A1C level less than 7 percent for most patients with diabetes.2
Dr. Steinberg challenges this goal and names three trials (UKPDS,3 ACCORD,4 and ADVANCE5) in support of his viewpoint. The UKPDS followed more than 3,500 participants with type 2 diabetes for 10 years and determined that tighter glycemic control reduced microvascular complications.3 The effect on coronary artery disease and stroke was equivocal at the conclusion of the trial. However, another study reported that cardiovascular and all-cause mortality was significantly reduced more than a dozen years after the conclusion of the original trial in the group with tighter glycemic control.6 Tighter blood pressure control also decreased cardiovascular and all-cause mortality in the UKPDS, one of many trials to confirm that controlling glucose in our patients with type 2 diabetes is inadequate without concurrent management of cardiovascular disease risk factors.
Two trials, ACCORD4 and ADVANCE,5 each enrolled more than 10,000 participants and sought to determine whether aggressively managing A1C to near-normal levels (level of a person without diabetes) would decrease macrovascular and/or microvascular outcomes compared with the current recommendations. In the ACCORD trial, the A1C goal for the intervention group was less than 6 percent. Although cardiovascular mortality was reduced, the study was discontinued when a small but significant increase in total mortality was discovered. In the ADVANCE trial, the A1C goal was 6.5 percent or less, and a nonsignificant trend toward increased total mortality was found for the intervention group.
These findings are not surprising given that the intervention groups had two- and threefold as many serious hypoglycemic events compared with the control groups, and hypoglycemia can precipitate complications from accidental injuries to fatal ischemia. An A1C of 7 percent corresponds to an average glucose level of 154 mg per dL (8.55 mmol per L). To achieve their A1C goal of less than 6.5 percent, participants in the ADVANCE trial needed an average glucose level less than 140 mg per dL (7.77 mmol per L), and participants in the ACCORD trial needed an average glucose level less than 126 mg per dL (6.99 mmol per L). An important hallmark of insulin resistance/type 2 diabetes is the elevation in postprandial blood glucose; attempting to achieve a low average glucose level when postmeal values are high can create significant fasting hypoglycemia.
Rather than refuting current guidelines, these trials provide support for the guidelines' cautionary statement that significant hypoglycemia should be avoided. Current evidence strongly suggests that encouraging a healthy lifestyle that includes physical activity and weight loss, aggressively managing cardiovascular disease risk factors, and normalizing blood glucose will provide the greatest benefit for our patients with type 2 diabetes.