The Effect of Long-Term Intensified Insulin Treatment on the Development of Microvascular Complications of Diabetes Mellitus

Abstract

A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established. We randomly assigned 102 patients with insulin-dependent diabetes mellitus, nonproliferative retinopathy, normal serum creatinine concentrations, and unsatisfactory blood glucose control to intensified insulin treatment (48 patients) or standard insulin treatment (54 patients). We then evaluated them for microvascular complications after 18 months and 3, 5, and 7.5 years. Mean (±SD) glycosylated hemoglobin values were reduced from 9.5 ±1.3 percent to 7.1 ±0.7 percent in the group receiving intensified treatment and from 9.4 ±1.4 percent to 8.5 ±0.7 percent in the group receiving standard treatment (P = 0.001). In 12 of the patients receiving intensified treatment (27 percent of those included in the analysis) and 27 of those receiving standard treatment (52 percent), serious retinopathy requiring photocoagulation developed (P = 0.01). Visual acuity decreased in 6 patients receiving intensified treatment (14 percent) and in 18 receiving standard treatment (35 percent) (P = 0.02). Nephropathy (urinary albumin excretion, >200 μg per minute) developed in one patient in the group receiving intensified treatment, as compared with nine patients in the group receiving standard treatment (P = 0.01). No patient in the intensified-treatment group had nephropathy with subnormal glomerular filtration rates, as compared with six patients in the standard-treatment group (P = 0.02). The conduction velocities of the ulnar, tibial, peroneal, and sural nerves decreased significantly more in the standard-treatment group than in the intensified-treatment group. The odds ratio for serious retinopathy was 0.4 (95 percent confidence interval, 0.2 to 1.0; P = 0.04) in the intensified-treatment group as compared with the standard-treatment group. The corresponding odds ratio for nephropathy was 0.1 (95 percent confidence interval, 0 to 0.8; P = 0.04). Long-term intensified insulin treatment, as compared with standard treatment, retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus., Microvascular complications develop in many patients with insulin-dependent diabetes mellitus, and the effect of intensified insulin treatment on these complications has not been established. Some prospective, randomized studies have indicated that lower blood glucose concentrations retard the progression of nephropathy1–6 and neuropathy,5,7 but not that of retinopathy3,8–11. The Stockholm Diabetes Intervention Study was initiated in 1982 to compare the effects of intensified insulin treatment and standard insulin treatment on these complications. The results of this study after 18 months,12 3 years,13,14 and 5 years15–17 have been published. They show that albuminuria, the deterioration… © 1993, Massachusetts Medical Society. All rights reserved.