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Glycemic control and vascular complications in type 2 diabetes mellitus

Author
David K McCulloch, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

The importance of tight glycemic control for protection against microvascular and cardiovascular disease in diabetes was established in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study for type 1 diabetes [1,2]. Although the role of glycemic control on microvascular disease in type 2 diabetes was documented in the United Kingdom Prospective Diabetes Study (UKPDS), its role in reducing cardiovascular risk has not been established as clearly for type 2 diabetes.

The effects of glycemic control on microvascular and macrovascular complications in type 2 diabetes will be reviewed here. Glycemic control and vascular complications in type 1 diabetes, the mechanism by which hyperglycemia might cause these complications, and an overview of the treatment of diabetes are discussed separately. (See "Glycemic control and vascular complications in type 1 diabetes mellitus" and "Overview of medical care in adults with diabetes mellitus".)

MICROVASCULAR DISEASE

Hyperglycemia is an important risk factor for the development of microvascular disease in patients with type 2 diabetes, as it is in patients with type 1 diabetes. This has been shown in several observational studies [3,4]. In addition, improving glycemic control improves microvascular outcomes, as illustrated by the findings of a meta-analysis of randomized trials (34,912 participants) [5]. There was a reduction in the risk of microvascular complications (a composite outcome including progression of nephropathy, manifestation and progression of retinopathy, and retinal photocoagulation) in the intensive compared with standard glycemic control group (relative risk [RR] 0.88, 95% CI 0.82-0.95). There were significant reductions in risk for each of the individual components.

In another meta-analysis of 7 trials (28,065 adults) evaluating the benefits of intensive versus conventional glycemic control specifically on renal outcomes, there was a statistically significant reduction in the risk of microalbuminuria and macroalbuminuria in patients randomly assigned to intensive glycemic control (risk ratios of 0.86 and 0.74, respectively) [6]. The reduction in risk of end stage renal disease did not reach statistical significance (RR 0.69, 95% CI 0.46-1.05). There was no reduction in the risk of doubling of the serum creatinine level or death from renal disease (RRs 1.06 and 0.99, respectively). Of note, the majority of the trials in the meta-analysis were not of long enough duration to show a beneficial effect of glycemic control on end stage renal disease, which typically manifests after 10 to 20 years of diabetes duration [7]. In the trials included in the meta-analysis, the absolute rates of severe renal outcomes were low in both the intensive and conventional therapy groups, reducing the ability of the analysis to demonstrate a benefit, if one exists. In the one trial with longer-term follow-up (United Kingdom Prospective Diabetes Study [UKPDS] cohort followed for 22 years), there was a beneficial effect of intensive therapy on the development of more advanced clinical outcomes, including renal disease [8]. (See 'Post-trial monitoring' below.)

The major trials are described below:

                      

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Literature review current through: Nov 2016. | This topic last updated: Wed Mar 09 00:00:00 GMT+00:00 2016.
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