Although microvascular complications such as retinopathy, nephropathy and neuropathy cause significant morbidity and mortality, preventive efforts in type 2 diabetes (formerly known as non–insulin-dependent diabetes) have concentrated on prevention of heart disease, stroke and other macrovascular events. Gæde and colleagues investigated the ability of intensive behavior and pharmacologic therapy to slow progression of microvascular complications in high-risk patients with type 2 diabetes as evidenced by microalbuminuria.

Study subjects were recruited from a Danish diabetes clinic. All of the patients met World Health Organization diagnostic criteria for type 2 diabetes, and microalbuminuria was identified by at least four of six urine samples. Patients were randomly assigned to either standard treatment following the recommendations of the Danish Medical Association or to intensive management that incorporated behavior modification and stepwise pharmacologic therapy designed to maximize glucose control and compliance.

All participants received individualized dietary advice. Patients in the intensive-intervention group were counseled to stop smoking and to participate in 30 minutes of light to moderate exercise three to five times per week. Regardless of blood pressure, intensive-intervention patients received an angiotensin-converting enzyme (ACE) inhibitor in a dosage equivalent to 50 mg of captopril twice daily. These patients also received 250 mg of vitamin C and 100 mg of vitamin E, with the intake increased fivefold for those who continued to smoke. Patients with a history of cardiovascular disease were given 150 mg of aspirin daily.

If the hemoglobin A_1C (HbA_1C) level could not be suitably maintained by diet alone after a three-month trial, hypoglycemic agents were added to the therapeutic regimen, and the dosage was titrated to obtain glycemic control. If combinations of maximum dosages of oral agents failed to bring HbA_1C levels within the acceptable range, insulin therapy was substituted for oral hypoglycemic agents. If blood pressure was not adequately controlled by ACE inhibitors, stepwise therapy introducing other agents was used until control was obtained. Statin drugs were used to reduce elevated cholesterol levels, and fibrates were used to reduce elevated triglyceride levels.

In the intensive-therapy group, 73 of 80 randomized patients completed approximately four years of follow-up, compared with 76 of 80 patients assigned to standard therapy. Nephropathy developed in eight patients in the intensive-intervention group, compared with 19 of the usual-care patients. Progression of retinopathy was documented in 19 of the intensive-care patients and in 33 of those treated routinely. Eight of the intensively treated patients and 22 of those in the standard-therapy group had progression of autonomic neuropathy.

The authors conclude that intensive multi-factorial intervention may be sustained over several years and may significantly slow progression of the microvascular complications of type 2 diabetes.