title: The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus.
abstract: BACKGROUND
  A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 micrograms 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).
  
  
  CONCLUSIONS
  Long-term intensified insulin treatment, as compared with standard treatment, retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus.
authors.affiliation: Department of Internal Medicine, Södersjukhuset, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Reichard
authors.forename: B Y
authors.initials: BY
authors.lastname: Nilsson
authors.forename: U
authors.initials: U
authors.lastname: Rosenqvist
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000209:etiology / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000209:etiology / Q000517:prevention & control; D005500:Follow-Up Studies; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D016017:Odds Ratio
chemical_list: D001786:Blood Glucose; D007328:Insulin