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Intensive insulin therapy reduced microvascular outcomes in patients with type 1 diabetes and nonproliferative retinopathy

ACP J Club. 1994 Mar-April;120:31. doi:10.7326/ACPJC-1994-120-2-031

Source Citation

Reichard P, Nilsson B, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993 Jul 29;329:304-9.



To evaluate the effectiveness of intensified insulin treatment in reducing chronic microvascular complications in patients with type 1 diabetes mellitus.


Randomized controlled trial with 7.5 years of follow-up.


Clinical center in Sweden.


102 patients (mean age 31 y, 53% men) with type 1 diabetes, nonproliferative retinopathy, normal serum creatinine levels, and unsatisfactory blood glucose control. Patients with albuminuria were not excluded. Follow-up was 87%.


48 patients were allocated to receive intensified treatment, which consisted of individual education and then continuing tutoring with frequent face-to-face and telephone contact initially every 2 weeks, then at greater intervals. 54 patients received standard treatment, which consisted of routine diabetes care (visiting the physician every 4 mo).

Main outcome measures

Retinopathy, nephropathy, and neuropathy evaluated after 1.5, 3, 5, and 7.5 years.

Main results

82% of patients receiving intensified therapy took ≥ 3 insulin injections daily. During the first 5 years, most patients in the standard-treatment group took 2 daily insulin injections. Mean glycosylated hemoglobin was 7.1% in the intensified-treatment group and 8.5% in the standard-treatment group (normal range 3.9% to 5.7%). Fewer patients in the intensified-treatment group, compared with the standard-treatment group, developed serious retinopathy (P = 0.01), had decreased visual acuity (P = 0.02), and had nephropathy (P = 0.01) (Table). The number of patients with symptoms of peripheral neuropathy increased from 5 to 6 in the intensified-treatment group and from 8 to 13 in the standard-treatment group (P = 0.1 for the difference between groups). The deterioration in nerve conduction velocities was greater in the standard-treatment group (P = 0.003 for the tibial nerve, P = 0.007 for the peroneal nerve, and P = 0.02 for the sural nerve).


Intensified insulin treatment retarded both mild and advanced microvascular complications in patients with type 1 diabetes mellitus and nonproliferative retinopathy.

Sources of funding: NOVO-Nordisk; Boehringer-Mannheim Scandinavia; Swedish Medical Research Council.

For article reprint: Dr. P. Reichard, Department of Internal Medicine, Södersjukhuset, 118 83 Stockholm, Sweden. FAX 46-8-616-3117.

Table. Intensified vs standard therapy at 5 years in type 1 diabetes*

Outcomes at 5 y Intensified treatment Standard treatment RRR (95% CI) NNT (CI)
Serious retinopathy 27% 52% 47% (12 to 70) 4 (2 to 20)
Decreased visual acuity 14% 35% 61% (14 to 83) 5 (3 to 27)
Nephropathy 2% 17% 87% (25 to 98) 7 (4 to 29)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Intensive insulin therapy reduced microvascular and neurologic outcomes in type I diabetes mellitus

All who routinely care for patients with diabetes can sigh with relief because now there are good experimental data to support our long-held belief that intensive treatment of diabetes leads to reduced risk for microvascular complications. But the sigh can only be brief because our responsibilities to our patients have now been considerably increased and, for many of us, it is not clear whether resources necessary to achieve these results are available.

The DCCT was an efficacy, not an effectiveness, trial. In the optimal conditions of this trial, with highly motivated patients and specially trained treatment team members, microvascular disease progression was slowed. The study by Reichard and colleagues also included much more interaction with patients than occurs in usual practice settings. Can we achieve the same results in our own practices? Perhaps.

What are the "take home" messages? First, to achieve these results, a long-term strategy would have to be adopted; it took 36 months for the groups to diverge, and, in both the DCCT and the study by Reichard and colleagues, existent retinopathy worsened early in the trial. Second, complete prevention of complications may require absolute normalization of glucose from the day of diagnosis because even the intensive-treatment group developed some complications. It is important to note, however, that lowering of the glucose to some degree still achieved partial reduction in complications. Third, intensive therapy is costly from both a human point of view and a monetary point of view: The incidence of severe hypoglycemia was increased and patients were contacted frequently by study personnel. Cost-effectiveness analyses from the DCCT show an additional cost of $33 746 over a lifetime for intensive compared with conventional therapy. The cost per year of life saved is $28 661, which is considered to be cost-effective.

The United Kingdom Prospective Diabetes Study, which was completed in 1998, has extended these results to patients with type 2 diabetes who use a variety of treatments. Glycemic control should be a high priority for persons with diabetes, whether type 1 or 2, based on these 2 large, long-term trials.

Finally, physicians and nurses treating patients with diabetes need to take a proactive role in initiating change in our usual patterns of diabetic care. Our treatment community is not consistently doing simple things to prevent complications, such as screening regularly for retinopathy or examining feet to prevent amputations. We must strive to address all the prevention and screening needs of our patients with diabetes in addition to improving glucose control. We also need to become active in the political process to ensure that funds are sufficient to support the nursing care, equipment, supplies, and education required to achieve our new and more ambitious goals.

Jacqueline A. Pugh, MD
The University of TexasSan Antonio, Texas, USA


1. The Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial.JAMA. 1996;276:1409-15