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


5-year effects of intensified insulin for diabetes

ACP J Club. 1992 Jan-Feb;116:5. doi:10.7326/ACPJC-1992-116-1-005

Source Citation

Reichard P, Berglund B, Britz A, et al. Intensified conventional insulin treatment retards the microvascular complications of insulin-dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years. J Intern Med. 1991 Aug;230:101-8.



To evaluate the long-term effect on microvascular complications of intensified conventional treatment for insulin-dependent diabetes in patients with unsatisfactory blood glucose control.


Randomized trial of 5 years duration.


Not stated.


102 patients with insulin-dependent diabetes, nonproliferative retinopathy, normal serum creatinine levels, and unsatisfactory blood glucose control were included. 96 patients (mean age at study entry, 31.2 years; duration of diabetes, 17.0 years; 49 men) were followed for 5 years.


Patients were assigned to intensified conventional treatment (ICT; n = 44) or to regular treatment (RT; n = 52). ICT included education, change to multiple insulin injections, and self-blood-glucose monitoring.

Main outcome measures

Mean glycated hemoglobin (HbA1c; normal range, 3.9% to 5.7%), retinal photographs, urinary albumin excretion rates, nerve conduction velocity, and autonomic nerve testing.

Main results

Mean HbA1c fell during the study from 9.5% to 7.2% in the ICT group and from 9.4% to 8.7% in the RT group (P < 0.001). Retinopathy increased in both groups, but after 5 years it was worse in the RT group (P < 0.05). The frequency of proliferative retinopathy did not differ. 8 RT patients developed manifest nephropathy (defined as urinary albumin ≥ 200 µg/min), compared with none in the ICT group (P < 0.01). Nerve conduction velocities were lower in the RT group (P < 0.05). Neuropathy was more frequent in RT patients (34 cases) compared with 16 ICT patients (P < 0.01). The increases in retinopathy (odds ratio [OR], 2.2; 95% CI, 1.3 to 3.7; P < 0.01), albuminuria (OR, 2.3; CI, 1.3 to 3.4; P < 0.01), and neuropathy (OR, 3.5; CI, 1.7 to 7.0; P < 0.001) were all related to the mean HbA1c level during the study but not to prestudy levels. Hypoglycemia requiring assistance occurred in 34 ICT patients (77%; CI, 65% to 89%) and 29 RT patients (56%; CI, 43% to 69%): 242 and 98 episodes, respectively (P < 0.05). 4 patients in the ICT group and 1 patient in the RT group died; they did not differ from the surviving patients in progression of complications. Mean weight for the ICT group increased 4.1 kg whereas the RT group maintained stable weight.


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

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

Address for article reprint: Dr. P. Reichard, Medical Clinic II, Södersjukhuset, 3-100 64 Stockholm, Sweden.


This study supports the finding of decreased major microvascular complications of insulin-dependent diabetes mellitus with an intensified manual insulin regimen. This finding is consistent with observations that diabetic retinopathy may worsen transiently, but in the long term will progress more slowly in patients with tighter glycemic control (1). Similarly, albuminuria appears to be decreased in tightly controlled diabetics independent of other factors (e.g., hypertension).

The study may underestimate these benefits, given that 42% of the regular treatment (RT) group used 3 to 6 injections daily, which indicated intensive therapy in this group as well. The similarity of the treatment regimens was reflected in the modest intergroup difference in HbA1c (7.2% vs. 8.7%). Determining the exact effect of intensified insulin therapy is difficult because the intervention was not clearly explained and the antihypertensive agents used were not defined for both groups and might have affected albuminuria differently. Finally, albuminuria cannot be equated with nephropathy as assumed here (2).

Still unknown is whether a reduction in these complications translates into a longer life expectancy and an improved quality of life because of the greater threat of hypoglycemia with tighter glycemic control (3). To achieve tight glycemic control, patients must do multiple blood glucose determinations daily and must make decisions on altering insulin doses. This requires a great amount of discipline, time, and expense, and may even result in increased mortality. Further study is required before changes in current management of these patients can be suggested.

Carolyn Pedley, MD
Robert Bloomfield, MD Bowman Gray Medical School Winston-Salem, North Carolina