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


Therapeutics

Review: Intensive blood-glucose control reduces diabetic complications in patients with insulin-dependent diabetes mellitus

ACP J Club. 1993 Nov-Dec;119:71. doi:10.7326/ACPJC-1993-119-3-071


Source Citation

Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet. 1993 May 22;341:1306-9.


Abstract

Objective

To determine, using meta-analysis, the effect of intensive therapy for blood-glucose control on retinopathy, nephropathy, and side effects in adults with insulin-dependent diabetes mellitus (IDDM).

Data sources

{English-language, randomized controlled trials were identified using MEDLINE from 1966 to 1991, conference abstracts, and bibliographies of relevant studies and review articles. Search terms were diabetes and insulin. Author searches were also done.}*

Study selection

Studies were selected if they were the latest report of a study, the patients studied had IDDM, and data were sufficient for analysis.

Data extraction

Numbers of patients enrolled, differences in blood glucose and blood pressure levels, numbers of patients with deterioration of retinopathy or nephropathy, and incidence of diabetic ketoacidosis and severe hypoglycemia were extracted. Nephropathy progression was defined as increased urinary albumin excretion.

Main results

32 studies were identified and 16 (from 12 cohorts) were selected for meta-analysis. Conventional glucose control included 1 or 2 daily injections of insulin. Intensive therapy was obtained with continuous subcutaneous infusion or by multiple injections of insulin, except for 1 study that used 2 or 3 daily insulin injections. Follow-up ranged from 8 to 60 months. All but 1 study had better or nearly normal glucose control with intensive therapy. Glycosylated hemoglobin was 1.4% lower (95% CI -1.8% to -1.1 %) with intensive therapy. Blood pressure did not differ between the groups. A nonsignificant trend was noted toward worsening retinopathy in patients receiving intensive therapy for 6 to 12 months. After 2 to 5 years of therapy, the risk for diabetic retinopathy progression was reduced with intensive therapy (odds ratio [OR] 0.49, CI 0.28 to 0.85, P = 0.011) and for development of severe retinopathy (OR 0.44, CI 0.22 to 0.87, P = 0.02). Patients receiving intensive therapy also had a reduced risk for progression of diabetic nephropathy (OR 0.34, CI 0.20 to 0.58, P < 0.001). Findings for retinopathy and nephropathy were consistent across studies (tests for heterogeneity were not significant). A nonsignificant trend toward more frequent severe hypoglycemic reactions occurred in patients who received intensive therapy. Patients treated with continuous subcutaneous insulin infusion had 12.6 more episodes of ketoacidosis per 100 patient-years (CI 8.7 to 16.5) than did patients in the control groups (3 studies).

Conclusions

Intensive blood-glucose control reduces glycoslyated hemoglobin, nephropathy, and long-term retinopathy in patients with insulin-dependent diabetes. Side effects are also increased.

Source of funding: Agency for Health Care Policy and Research.

For article reprint: Dr. P.H. Wang, Joslin Diabetes Center, One Joslin Place, Boston MA 02215, USA. FAX 617-732-2593.

*Information supplied by author.


Commentary

Using meta-analysis methods, Wang and colleagues examined a fundamental question in diabetes research: What are the benefits and risks of intensive blood-glucose control in IDDM? Their analysis adds to the growing evidence that intensive therapy decreases the risk for chronic complications of diabetes. It is interesting, however, that the meta-analysis did not detect an increase in severe hypoglycemia with intensive therapy. This may have resulted from incomplete ascertainment of severe hypoglycemic episodes in the studies included in the meta-analysis. Conclusive data now exist documenting a significant 3-fold increase in severe hypoglycemia with intensive therapy (1).

Meta-analysis is a useful method of examining data from various studies using objective grading criteria with the principal aim of increasing sample size and thus improving statistical power. In the context of blood-glucose control and the complications of diabetes, it is important to note that the total number of patients in the meta-analysis is less than 20% of the 1441 patients studied in the Diabetes Control and Complications Trial (DCCT). The DCCT is also unique in that it examines the effect of glycemic control both on primary and secondary intervention.

It is evident that for most patients with IDDM, the benefits of intensive therapy in preventing the development and alleviating the progression of the long-term microvascular complications (by approximately 50%) far outweigh the known risks (2). As with any treatment, specific management goals must be established on an individual basis. Nonetheless, the importance and benefits of achievng near-normal glycemic regulation have now been clearly established.

Bernard Zinman, MD
University of TorontoToronto, Ontario, Canada


References

1. The DCCT Research Group. Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med. 1991;90:450-9.

2. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-86.