to the editor: I wish to expand on several points in a recent article on reducing the complications in type 2 (non-insulin–dependent) diabetes.¹ The authors cite the results of the Diabetes Control and Complications Trial (DCCT), which studied glycemic control in patients with type 1 (insulin-dependent) diabetes, and discuss its implications for patients with type 2 diabetes. However, there is now a similar study of glycemic control performed in patients with type 2 diabetes that is more relevent to other patients with type 2 diabetes.² The study randomized 110 patients with type 2 diabetes to intensive or conventional insulin treatment for six years and found reductions in nephropathy, retinopathy and neuropathy that were similar to those found in the DCCT.² The glycemic threshold to prevent these complications was a hemoglobin A_1c level less than 6.5 percent.

Though glycemic control is important, the importance of blood pressure control, at least in the prevention of diabetic nephropathy, cannot be overemphasized. The goal for patients with type 2 diabetes is to maintain a blood pressure less than 130/85 mm Hg, with further reductions as tolerated.³ Angiotensin-converting enzyme (ACE) inhibitors are recommended as first-line therapy for antihypertensive treatment, since they lower glomerular capillary pressure and preserve glomerular filtration rate more than can be explained by their blood pressure effects alone.⁴

In one important ACE inhibitor study, Ravid and colleagues⁵ randomized 94 patients with type 2 diabetes who were normotensive and had normal renal function and microalbuminuria to enalapril maleate (Vasotec), in a dosage of 10 mg per day or placebo, and followed them over five years. While the enalapril group's average protein excretion remained stable at approximately 140 mg per 24 hours, the placebo group's protein excretions increased from 123 to 310 mg per 24 hours.⁵ The American Diabetes Association (ADA) supports the use of ACE inhibitors when type 2 diabetes is accompanied by microalbuminuria and normal blood pressure; for those who have progressed from microalbuminuria to proteinuria, the ADA also recommends dietary protein reductions to 0.8 g per kg per day or 10 percent of calories.³

The recent lowering of the fasting blood glucose cutoff for diagnosing diabetes to 126 mg per dL (6.9 mmol per L)⁶ or greater should allow for earlier diagnosis of diabetes and more effective secondary prevention of complications. Recently, the NIH has launched a multicenter primary prevention trial, the Diabetes Prevention Program (DPP), to find the best way to prevent type 2 diabetes. Successful primary prevention could be the most effective method yet of reducing the microvascular complications of diabetes. While we await the results of the DPP, efforts should be focused on the screening of high risk individuals with fasting blood sugars, the aggressive control of blood pressure and blood sugar and the appropriate use of ACE inhibitors in patients with type 2 diabetes.

in reply: We appreciate Dr. Poirier's comments on our article and wish to briefly clarify several important points. Ohkubo and colleagues¹ do provide significant additional evidence for our assertion that microvascular complications in type 2 diabetes are linked to hyperglycemia. However, this study is limited by the small sample size (110 patients) and the inclusion of only nonobese, Japanese, insulin-treated patients. This study also fails to resolve the question of the effects of tighter glycemic control using insulin on macrovascular complications.

We do agree with Dr. Poirier's emphasis on the importance of controlling blood pressure and preventing nephropathy. Nonetheless, we continue to believe that a patient-centered approach may necessitate trade-offs between ideal biomedical management and patient preferences. As Dr. Poirier suggests, the lowering of the fasting blood glucose cutoff for diagnosing diabetes to 126 mg per dL (6.9 mmol per L) or greater will provide an opportunity to diagnose diabetes earlier.² We hope physicians can use this extra lead time to educate their patients, to gain a better understanding of their priorities and to facilitate negotiation of mutually agreed upon goals for management.