From the Editorial Board: I thought I knew how to manage diabetes

I hate to admit it, but I'm terribly confused.

I thought I understood how to manage diabetes. While each patient is different, caring for diabetic patients, like breathing, is what we do daily. Clearly, the irrefutable benefits of tighter diabetes control with respect to microvascular disease (nephropathy, neuropathy, and retinopathy) were demonstrated years ago with the DCCT¹ and UKPDS² trials. While these landmark studies didn't definitively prove that macrovascular complications would decrease, a follow-up study of the original DCCT cohort assigned to tighter glycemic control had better macrovascular outcomes over time, even though differences in control between groups diminished after termination of the study.³

Based on this seemingly incontrovertible proof, unless contraindicated because of severe comorbidity or history of profound and symptomatic hypoglycemic events, I diligently—almost slavishly—followed the American Diabetes Association (ADA) guidelines and targeted a goal hemoglobin A_1c (HbA_1c) <7% for diabetic patients under my care. Through my Veterans Administration's (VA) quality-management office, I assiduously distributed lists of diabetes patients whose HbA_1c was above this goal to providers on my health-care team and expected them to intensify therapy in most of these patients (as I was doing). Not only did I selfishly want my team to have the best control in the VA system, but I truly thought it was clinically justified.

Within the past year, three major studies looking at the relationship between tighter diabetes control and macrovascular disease have been published: The ACCORD,⁴ ADVANCE,⁵ and VA Diabetes⁶ trials. They have iconoclastically shattered the myth that near-normal control equates to universally better outcomes. In fact, not only did the VA study fail to show improvement in several microvascular outcomes, but the ACCORD study had to be terminated early because of increased mortality in the cohort randomized to near-normal control. Not unexpectedly, these studies showed higher rates of hypoglycemic episodes in the more intensively treated groups.

It was with much enthusiasm that I read the recently published position statement of the ADA,⁷ and I sincerely encourage all physicians to do the same. The ADA “spin” is that previous studies provided unassailable evidence regarding improved microvascular outcomes with tighter glycemic control. The new studies didn't show improved macrovascular outcomes, says the ADA, because they included subjects with long-established diabetes mellitus, who probably already suffered occult macrovascular disease prior to enrollment.

While the ADA tempers its enthusiasm to aim for an HbA_1c < 7% in all diabetic patients, it does state that these studies do “not suggest the need for major changes in glycemic control targets, but rather, additional clarification of the language that has consistently stressed individualization.”

I'm probably going to be less likely than I was in the past to increase the hypoglycemic regimen of the next elderly veteran patient I see with an HbA_1c of 7.3%. I'm interested in your take—please use the comment box below to post your thoughts. Unless convincing evidence exists to clarify muddled thoughts, confusion, like misery, loves company.

Dr. Federman is firm chief, primary care, West Haven VA Hospital, West Haven, Conn., and  professor of medicine, Yale University School of Medicine. He is a member of the Cortlandt Forum Editorial Board.

References

1. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986. Available at content.nejm.org/cgi/content/full/329/14/977?ijkey=a7d54236b50c346440bbd6cb3b1a17d46ad1ff57, accessed February 18, 2009.

2. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.

3. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643-2653. Available at content.nejm.org/cgi/content/full/353/25/2643, accessed February 19, 2009.

4. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559. Available at content.nejm.org/cgi/content/full/358/24/2545, accessed February 18, 2009.

5. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2572. Available at content.nejm.org/cgi/content/full/358/24/2560, accessed February 18, 2009.

6. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-139. Available at content.nejm.org/cgi/content/full/360/2/129, accessed February 18, 2009.

7. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials. A position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care. 2009;32:187-192. Available at care.diabetesjournals.org/cgi/content/full/32/1/187, accessed February 18, 2009.