Curriculum in Cardiology
Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: Meta-analysis of randomized trials

https://doi.org/10.1016/j.ahj.2005.09.015Get rights and content

Background

Uncertainty persists concerning the effect of improved long-term glycemic control on macrovascular disease in diabetes mellitus (DM).

Methods

We performed a systematic review and meta-analysis of randomized controlled trials comparing interventions to improve glycemic control with conventional treatment in type 1 and type 2 diabetes. Outcomes included the incidence rate ratios for any macrovascular event, cardiac events, stroke, and peripheral arterial disease, and the number needed to treat intensively during 10 years to prevent one macrovascular event.

Results

The analysis was based on 8 randomized comparisons including 1800 patients with type 1 DM (134 macrovascular events, 40 cardiac events, 88 peripheral vascular events, 6 cerebrovascular events, 11 293 person-years of follow-up) and 6 comparisons including 4472 patients with type 2 DM (1587 macrovascular events, 1197 cardiac events, 87 peripheral vascular events, 303 cerebrovascular events, 43 607 person-years). Combined incidence rate ratios for any macrovascular event were 0.38 (95% CI 0.26-0.56) in type 1 and 0.81 (0.73-0.91) in type 2 DM. In type 1 DM, effect was mainly based on reduction of cardiac and peripheral vascular events and, in type 2 DM, due to reductions in stroke and peripheral vascular events. Effects appear to be particularly important in younger patients with shorter duration of diabetes.

Conclusions

Our data suggest that attempts to improve glycemic control reduce the incidence of macrovascular events both in type 1 and type 2 DM. In absolute terms, benefits are comparable, although effects on specific manifestations of macrovascular disease differ.

Section snippets

Literature search and eligibility criteria

We aimed to identify all randomized controlled comparisons of improved glycemic control that assessed macrovascular disease in types 1 and 2 DM. Using Cochrane methodology,15 we searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for relevant studies. We considered studies in any language. Electronic searches were supplemented by hand-searching of reference lists, reviews, relevant book chapters, conference abstracts, and specialist journals. We evaluated each study for

Identification of eligible studies and comparisons

We screened 1438 reports and excluded 1313. The remaining 125 reports, which reported on 14 different studies, were retrieved for detailed evaluation. Ten studies that included 14 randomized comparisons of intensified and conventional treatment were included (Figure 1). Eight comparisons had been performed in patients with type 1 DM5, 7, 8, 10, 11, 12 and 6 in patients with type 2 DM.6, 9, 22, 23 The DCCT in patients with type 1 DM5 and the Kumamoto study in patients with type 2 DM9 included 2

Discussion

In this systematic review and meta-analysis, we found that improved glycemic control translated into substantial reductions in macrovascular risk in type 1 DM while producing a smaller reduction in patients with type 2 DM. In type 1 DM, important beneficial effects were evident for cardiac and peripheral vascular events. In type 2 DM, substantial effects were observed for peripheral vascular disease and stroke, whereas cardiac events were not found to be reduced significantly. Of note, the

References (43)

  • P. Reichard et al.

    Mortality and treatment side-effects during long-term intensified conventional insulin treatment in the Stockholm Diabetes Intervention Study

    Diabetes

    (1994)
  • M. Shichiri et al.

    Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients

    Diabetes Care

    (2000)
  • A. Verrillo et al.

    Long-term correction of hyperglycemia and progression of retinopathy in insulin dependent diabetes. A five-year randomized prospective study

    Diabetes Res

    (1988)
  • Intensive therapy and progression to clinical albuminuria in patients with insulin dependent diabetes mellitus and microalbuminuria. Microalbuminuria Collaborative Study Group, United Kingdom

    BMJ

    (1995)
  • Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial

    Am J Cardiol

    (1995)
  • M. Egger et al.

    Meta-analysis: potentials and promise

    BMJ

    (1997)
  • K.A. Robinson et al.

    Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed

    Int J Epidemiol

    (2002)
  • P. Juni et al.

    Systematic reviews in health care: assessing the quality of controlled clinical trials

    BMJ

    (2001)
  • J.P. Higgins et al.

    Quantifying heterogeneity in a meta-analysis

    Stat Med

    (2002)
  • D.G. Altman

    Confidence intervals for the number needed to treat

    BMJ

    (1998)
  • M. Egger et al.

    Bias in meta-analysis detected by a simple, graphical test—authors reply

    BMJ

    (1998)
  • Cited by (405)

    View all citing articles on Scopus

    We declare that we have no conflict of interest. This study was supported by grants from Novo Nordisk, Küsnacht, Switzerland, Roche Diagnostics, Rotkreuz, Switzerland, and Glaxo Smith Kline, Münchenbuchsee, Switzerland.

    View full text