Current issues of ACP Journal Club are published in Annals of Internal Medicine


Intensified insulin for diabetes

ACP J Club. 1991 Mar-April;114:44. doi:10.7326/ACPJC-1991-114-2-044

Source Citation

Reichard P, Britz A, Carlsson P, et al. Metabolic control and complications over 3 years in patients with insulin dependent diabetes (IDDM): the Stockholm Diabetes Intervention Study (SDIS). J Intern Med. 1990;228:511-7.



To evaluate the effectiveness of intensified conventional treatment for insulin-dependent diabetes (IDDM) in patients with unsatisfactory blood glucose control, when compared with regular treatment.


Randomized trial of 3 years' duration.


Not stated.


Patients with type 1 diabetes, nonproliferative retinopathy without previous photocoagulation, normal serum creatinine levels, and unsatisfactory blood glucose control were included. Of the 102 patients selected for the study, 97 were followed for 3 years. The mean age of patients was 30.5 years with a mean duration of diabetes of 17.0 years.


Assignment to intensified conventional treatment (ICT, n = 44) or regular treatment (RT, n = 53). ICT included education, change to multiple insulin injections, self-blood-glucose monitoring, and easy access to a physician. The goal of regular treatment was to reduce blood glucose levels.

Main outcome measures

Glycosylated hemoglobin levels (HbA1C; normal range, 3.9% to 5.7%) and occurrence or progression of retinopathy, nephropathy, and neuropathy.

Main results

During the study HbA1C fell from 9.5% at entry to 7.4% in the ICT group compared with a fall from 9.4% to 9.0% in the RT group (P < 0.001). Lower HbA1C levels were associated with reduced risk for microvascular complications (P = 0.01). Both groups showed increases in retinopathy (P < 0.001). The ICT group had somewhat less retinopathy at 18 months than the RT group (P = 0.03), but not at 36 months (P = 0.16). There was no difference in the frequency of proliferative retinopathy. Nerve conduction velocities at 36 months were impaired only in the RT group. 37 RT patients (73%; 95% CI, 61% to 84%) developed at least 1 microvascular complication compared with 22 ICT patients (50%; CI, 34% to 66%; P = 0.02). However, 57% of patients on intensified conventional treatment had at least 1 episode of hypoglycemia requiring third-party assistance or resulting in coma, compared with 23% in the regular treatment group (P = 0.001). 4 patients, randomized to ICT, died {Fisher's exact test, P = 0.12}.


Lower blood glucose levels achieved as a result of intensified conventional treatment slowed the progression of microvascular complications but at increased risk for hypoglycemia.

Sources of funding: The Swedish division of NOVO-Nordisk Inc.; Boehringer Mannheim Scand. Inc.; the Swedish Medical Research Council.

Address for article reprint: Dr. P. Reichard, Medical Clinic II, Södersjukhuset, S-100 64 Stockholm, Sweden.


This well-designed, well-executed but small study adds depth but not breadth to previously published randomized trials on intensive insulin therapy. Once again, glucose control is shown to correlate with progression of diabetic microvascular complications; intensive therapy does not reduce retinopathy compared with conventional therapy in those who start the therapy after retinopathy is established; and intensive therapy is shown to be associated with more severe hypoglycemia. And once again, the sample size is small.

The body of evidence supporting the relationship between glucose control and microvascular complications is now large. The primary remaining problem is to find a method of treatment capable of lowering glucose levels enough to prevent complications without causing serious adverse effects. At present, the only alternative to insulin injections for type 1 diabetics, pancreatic transplantation, is complicated by the need for immunosuppressive therapy, which also has serious side effects.

The Diabetes Control and Complications Trial (1), with its large sample size (1441), should help resolve the issue of whether the beneficial effects of this therapy outweigh the side effects. It should also help address whether intensive therapy can prevent retinopathy as well as slow the progression of established retinopathy. Given the serious side effects of this treatment, clinicians should be wary of prescribing intensive insulin treatment unless they can provide equally intensive support for these patients, including 24-hour-a-day access to physicians. Hirsch and colleagues (2) recently reviewed types of intensive regimens, their side effects, and benefits.

Jacqueline A. Pugh, MD
Audie L. Murphy Memorial Veterans Affairs Hospital San Antonio, Texas, USA